Urocortin protects chondrocytes from NO-induced apoptosis: a future therapy for osteoarthritis?

Intekhab Alam, N.Y., White, O.B., Getting, S.J., Petsa, A., Knight, R.A., Townsend, P.A., Lawrence, K.M. and Locke, I.C. 2013. Urocortin protects chondrocytes from NO-induced apoptosis: a future therapy for osteoarthritis? Cell Death and Disease. 4, p. e717.

TitleUrocortin protects chondrocytes from NO-induced apoptosis: a future therapy for osteoarthritis?
AuthorsIntekhab Alam, N.Y., White, O.B., Getting, S.J., Petsa, A., Knight, R.A., Townsend, P.A., Lawrence, K.M. and Locke, I.C.
Abstract

Osteoarthritis (OA) is characterized by a loss of joint mobility and pain resulting from progressive destruction and loss of articular cartilage secondary to chondrocyte death and/ or senescence. Certain stimuli including nitric oxide (NO) and the pro-inflammatory cytokine tumor necrosis factor α (TNF-α have been implicated in this chondrocyte death and the subsequent accelerated damage to cartilage. In this study, we demonstrate that a corticotrophin releasing factor (CRF) family peptide, urocortin (Ucn), is produced by a human chondrocyte cell line, C-20/A4, and acts both as an endogenous survival signal and as a cytoprotective agent reducing the induction of apoptosis by NO but not TNF-α when added exogenously. Furthermore, treatment with the NO donor S-nitroso-N-acetyl-D-L-penicillamine upregulates chondrocyte Ucn expression, whereas treatment with TNF-α does not. The chondroprotective effects of Ucn are abolished by both specific ligand depletion (with an anti-Ucn antibody) and by CRF receptor blockade with the pan-CRFR antagonist α-helical CRH(9-41). CRFR expression was confirmed by reverse transcription-PCR with subsequent amplicon sequence analysis and demonstrates that C-20/A4 cells express both CRFR1 and CRFR2, specifically CRFR1α and CRFR2β. Protein expression of these receptors was confirmed by western blotting. The presence of both Ucn and its receptors in these cells, coupled with the induction of Ucn by NO, suggests the existence of an endogenous autocrine/paracrine chondroprotective mechanism against stimuli inducing chondrocyte apoptosis via the intrinsic/mitochondrial pathway.

JournalCell Death and Disease
Journal citation4, p. e717
ISSN2041-4889
YearJul 2013
PublisherNature Publishing Group
FileGetting_et_al_2014.pdf
Digital Object Identifier (DOI)doi:10.1038/cddis.2013.231
Publication dates
PublishedJul 2013

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REV5901: the protective effect on bovine articular chondrocytes following single impact trauma
Nedelcheva, Y., Getting, S.J. and Kerrigan, M.J.P. 2010. REV5901: the protective effect on bovine articular chondrocytes following single impact trauma. Physiological Society Meeting 19. University of Manchester

REV5901: an investigation on the chondroprotective effect in bovine chondrocytes following single impact trauma
Nedelcheva, Y., Getting, S.J. and Kerrigan, M.J.P. 2010. REV5901: an investigation on the chondroprotective effect in bovine chondrocytes following single impact trauma. Physiological Society Meeting 21. University of Durham

The effect of indentor shape on the creep curves of collagen gel
Locke, I.C., White, O.B., Trwoga, P. and Afoke, A. 2010. The effect of indentor shape on the creep curves of collagen gel. OARSI 2010 World Congress on Osteoarthritis. Brussels, Belgium September 23-26, 2010

α-MSH and dTRP8-γ-MSH inhibit TNF-α induced MMP 1 and 13 expression in human C20/A4 chondrocytes
Kaneva, M., Locke, I.C., Kerrigan, M.J.P. and Getting, S.J. 2010. α-MSH and dTRP8-γ-MSH inhibit TNF-α induced MMP 1 and 13 expression in human C20/A4 chondrocytes. British Pharmacological Society Winter Meeting 2010. London, UK 14th-16th December 2010

Melanocortin peptides modulate pro-inflammatory mediator release from TNF-a stimulated C-20/A4 cells
Kaneva, M., Kerrigan, M.J.P., Locke, I.C. and Getting, S.J. 2010. Melanocortin peptides modulate pro-inflammatory mediator release from TNF-a stimulated C-20/A4 cells. British Orthopaedic Research Society Annual Meeting. Newcastle upon Tyne 22 - 23 Jun 2009 Wiley. pp. PO136

The MC3 agonist dTRP8-γ-MSH inhibits IL-6 and IL-8 release from TNF-α stimulated C-20/A4 chondrocytes, an effect blocked by the MC3R antagonist SHU9119
Kaneva, M., Kerrigan, M.J.P., Locke, I.C. and Getting, S.J. 2010. The MC3 agonist dTRP8-γ-MSH inhibits IL-6 and IL-8 release from TNF-α stimulated C-20/A4 chondrocytes, an effect blocked by the MC3R antagonist SHU9119. Physiology 2010. University of Manchester 30 June - 2 July 2010

Testicular LH-stimulated testosterone production is inhibited by activation of melanocortin 3 receptors (MC3)
Akindele, K., Horanin, M.M., Getting, S.J., Smith, C.L. and Murray, J.F. 2010. Testicular LH-stimulated testosterone production is inhibited by activation of melanocortin 3 receptors (MC3). Society for Reproduction and Fertility. Sutton Bonnington 11th - 13th July 2010

Anti-inflammatory and antiosteoclastogenesis propertiesof endogenous melanocortin receptor type 3 inexperimental arthritis
Patel, H.B., Bombardieri, M., Sampaio, A.L.F., D'Acquisto, F., Gray, M., Grieco, P., Getting, S.J., Pitzalis, C. and Perretti, M. 2010. Anti-inflammatory and antiosteoclastogenesis propertiesof endogenous melanocortin receptor type 3 inexperimental arthritis. FASEB Journal. 24 (12), pp. 4835-4843.

Melanocortin peptide therapy for the treatment of arthritic pathologies
Getting, S.J., Kaneva, M., Bhadresa, Y., Renshaw, D., Leoni, G., Patel, H.B., Kerrigan, M.J.P. and Locke, I.C. 2009. Melanocortin peptide therapy for the treatment of arthritic pathologies. The Scientific World Journal. 9, pp. 1394-1414.

Pro-inflammatory mediator release from TNF-α stimulated C-20/A4 cells results in Col II degradation
Kaneva, M., Kerrigan, M.J.P., Locke, I.C. and Getting, S.J. 2009. Pro-inflammatory mediator release from TNF-α stimulated C-20/A4 cells results in Col II degradation. British Orthopaedic Research Society (BORS) Annual Meeting. Newcastle 22nd - 23rd June 2009

The effects of REV5901 on chondrocyte viability following mechanical trauma
Parker, E., Getting, S.J., Hucklebridge, F., Vleck, V.E. and Kerrigan, M.J.P. 2009. The effects of REV5901 on chondrocyte viability following mechanical trauma. pA2 Online. From the Queen Elizabeth II Conference Centre London, Winter 2009 Meeting: Proceedings of the British Pharmacological Society. 7 (4), p. P0149.

Melanocortin peptides modulate pro-inflammatory mediator release from TNF-a stimulated C-20/A4 cells
Kaneva, M., Kerrigan, M.J.P., Locke, I.C. and Getting, S.J. 2009. Melanocortin peptides modulate pro-inflammatory mediator release from TNF-a stimulated C-20/A4 cells. pA2 Online. From the Queen Elizabeth II Conference Centre London, Winter 2009 Meeting: Proceedings of the British Pharmacological Society.

Molecular characterization of the melanocortin 3 receptor in the testes of mice
Horanin, M.M., Akindele, K., Getting, S.J., Smith, C.L. and Murray, J.F. 2009. Molecular characterization of the melanocortin 3 receptor in the testes of mice. pA2 Online. From the Queen Elizabeth II Conference Centre London, Winter 2009 Meeting: Proceedings of the British Pharmacological Society. 7 (4).

Inflamed phenotype of the mesenteric microcirculation of melanocortin type 3 receptor-null mice after ischemia-reperfusion
Leoni, G., Patel, H.B., Sampaio, A.L.F., Gavins, F.N.E., Murray, J.F., Grieco, P., Getting, S.J. and Perretti, M. 2008. Inflamed phenotype of the mesenteric microcirculation of melanocortin type 3 receptor-null mice after ischemia-reperfusion. FASEB Journal. 22 (12), pp. 4228-4238.

A role for MC3R in modulating lung inflammation
Getting, S.J., Riffo-Vasquez, Y., Pitchford, S., Kaneva, M., Grieco, P., Page, C.P., Perretti, M. and Spina, D. 2008. A role for MC3R in modulating lung inflammation. Pulmonary Pharmacology and Therapeutics. 21 (6), pp. 866-873.

Cardiac release of urocortin precedes the occurrence of irreversible myocardial damage in the rat heart exposed to ischemia/reperfusion injury
Knight, R.A., Chen-Scarabelli, C., Yuan, Z., McCauley, R.B., Di Rezzec, J., Scarabelli, G.M., Townsend, P.A., Latchman, D., Saravolatz, L., Faggian, G., Mazzucco, A., Chowdrey, H.S., Stephanou, A. and Scarabelli, T.M. 2008. Cardiac release of urocortin precedes the occurrence of irreversible myocardial damage in the rat heart exposed to ischemia/reperfusion injury. F E B S Letters. 582 (6), pp. 984-990.

Melanocortin 3 receptor in the testes of mice
Yogarajah, S., Lynch, S., Smith, C.L., Getting, S.J., Perretti, M. and Murray, J.F. 2008. Melanocortin 3 receptor in the testes of mice. Society for Reproduction and Fertility. Edinburgh 29 Jun - 01 Jul 2008 pp. Abstract P80

Melanocortin 3 receptor in the testes of mice
Wotherspoon, G., Yogarajah, S., Lynch, S., Smith, C.L., Getting, S.J., Perretti, M. and Murray, J.F. 2008. Melanocortin 3 receptor in the testes of mice. pA2 Online. From the University of Brighton, Winter 2008 Meeting: Proceedings of the British Pharmacological Society. 6 (4), p. P008.

Asymmetric dimethylarginine negatively influences osteoblast differentiation in vitro
Stenbeck, G., Joseph, J., Getting, S.J. and Smith, C.L. 2008. Asymmetric dimethylarginine negatively influences osteoblast differentiation in vitro. pA2 Online. From the University of Brighton, Winter 2008 Meeting: Proceedings of the British Pharmacological Society. 6 (4), p. C041.

The role of the actin cytoskeleton in chondrocyte protection following single impact
Nedelcheva, Y., Getting, S.J. and Kerrigan, M.J.P. 2008. The role of the actin cytoskeleton in chondrocyte protection following single impact. pA2 Online. From the University of Brighton, Winter 2008 Meeting: Proceedings of the British Pharmacological Society. 6 (4).

Tonic inhibitory control of the mesenteric microcirculation by the melanocortin type 3 receptor
Leoni, G., Patel, H.B., Sampaio, A.L.F., Gavins, F.N.E., Getting, S.J. and Perretti, M. 2008. Tonic inhibitory control of the mesenteric microcirculation by the melanocortin type 3 receptor. Journal of Vascular Research. 45 (Suppl2).

Inhibitory role of endogenous melanocortin type 3 receptor in the inflamed microcirculation
Leoni, G., Patel, H.B., Sampaio, A.L.F., Gavins, F.N.E., Getting, S.J. and Perretti, M. 2008. Inhibitory role of endogenous melanocortin type 3 receptor in the inflamed microcirculation. William Harvey Day. St. Barts Hospital, London 14th October 2008

A role for melanocortin peptides in modulating oxidative stress induced inflammation in A549 cells
Getting, S.J., Kaneva, M. and Kerrigan, M.J.P. 2008. A role for melanocortin peptides in modulating oxidative stress induced inflammation in A549 cells. pA2 Online. From the University of Brighton, Winter 2008 Meeting: Proceedings of the British Pharmacological Society. 6 (4), p. C020.

Melanocortins
Getting, S.J. 2008. Melanocortins. in: Offermanns, S. and Rosenthal, W. (ed.) Encyclopedia of molecular pharmacology. 2nd edition Berlin Springer. pp. 752-757

The effect of prolonged hypotonicity on chondrocyte volume regulation and intracellular calcium signalling
Ali, N., Getting, S.J. and Kerrigan, M.J.P. 2008. The effect of prolonged hypotonicity on chondrocyte volume regulation and intracellular calcium signalling. pA2 Online. From the University of Brighton, Winter 2008 Meeting: Proceedings of the British Pharmacological Society. 6 (4).

The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease
Abuirmeileh, A., Lever, R., Kingsbury, A.E., Lees, A.J., Locke, I.C., Knight, R.A., Chowdrey, H.S., Biggs, C.S. and Whitton, P.S. 2007. The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease. European Journal of Neuroscience. 26 (2), pp. 417-423.

Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery
Shah, C.M., Bell, S.E., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2007. Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery. Nitric Oxide. 16 (1), pp. 135-142.

Endogenous MC3R and inhibition of inflammatory arthritis. PC112
Patel, H.B., Sampaio, A.L.F., Getting, S.J., Gray, M. and Perretti, M. 2007. Endogenous MC3R and inhibition of inflammatory arthritis. PC112. Life Sciences. Glasgow 8th - 12th July 2007

Crucial role for endogenous melanocortin type 3 receptor in mesenteric post-reperfusion injury. PC106
Leoni, G., Getting, S.J., Gavins, F.N.E. and Perretti, M. 2007. Crucial role for endogenous melanocortin type 3 receptor in mesenteric post-reperfusion injury. PC106. Life Sciences. Glasgow 8th - 12th July 2007

Glucocorticoid and melanocortins: special issue
Getting, S.J. 2007. Glucocorticoid and melanocortins: special issue. ScientificWorldJournal. 7, pp. 1463-1464.

[D -Trp8]-γ -melanocyte -stimulating hormone exhibits anti-inflammatory efficacy in mice bearing a nonfunctional MC1 R(Recessive Yellow e/e Mouse)
Getting, S.J., Lam, C.W., Leoni, G., Gavins, F.N.E., Grieco, P. and Perretti, M. 2006. [D -Trp8]-γ -melanocyte -stimulating hormone exhibits anti-inflammatory efficacy in mice bearing a nonfunctional MC1 R(Recessive Yellow e/e Mouse). Molecular Pharmacology. 70 (6), pp. 1850-1855.

Annexin 1 and melanocortin peptide therapy for protection against ischaemic-reperfusion damage in the heart
Gavins, F.N.E., Leoni, G. and Getting, S.J. 2006. Annexin 1 and melanocortin peptide therapy for protection against ischaemic-reperfusion damage in the heart. ScientificWorldJournal. 6, pp. 1008-1023.

Cytotoxicity of clove (Syzygium aromaticum) oil and its major components to human skin cells
Prashar, A., Locke, I.C. and Evans, C.S. 2006. Cytotoxicity of clove (Syzygium aromaticum) oil and its major components to human skin cells. Cell Proliferation. 39 (4), pp. 241-248.

Targeting melanocortin receptors as potential novel therapeutics
Getting, S.J. 2006. Targeting melanocortin receptors as potential novel therapeutics. Pharmacology & Therapeutics. 111 (1), pp. 1-15.

Melanocortin receptor signaling in RAW264.7 macrophage cell line
Lam, C.W., Perretti, M. and Getting, S.J. 2006. Melanocortin receptor signaling in RAW264.7 macrophage cell line. Peptides. 27 (2), pp. 404-412.

The melanocortin peptide HP228 displays protective effects in acute models of inflammation and organ damage
Getting, S.J., Di Filippo, C., D'Amico, M. and Perretti, M. 2006. The melanocortin peptide HP228 displays protective effects in acute models of inflammation and organ damage. European Journal of Pharmacology. 532 (1-2), pp. 138-144.

Mode of glucocorticoid actions in airway disease
Ito, K., Getting, S.J. and Charron, C.E. 2006. Mode of glucocorticoid actions in airway disease. ScientificWorldJournal. 28 (6), pp. 1750-1769.

Mechanism of chondrocyte death in osteoarthritis
Intekhab Alam, N.Y. 2006. Mechanism of chondrocyte death in osteoarthritis. PhD thesis University of Westminster School of Life Sciences

Melanocortin 3 receptors control crystal-induced inflammation
Getting, S.J., Lam, C.W., Chen, A.S., Grieco, P. and Perretti, M. 2006. Melanocortin 3 receptors control crystal-induced inflammation. FASEB Journal. 20 (13), pp. 2234-2241.

Biological activity of industrial wood and bark waste from Pinus nigra
Curras Lino, M., Radman, R., Bertaud, F., Nisula, L., Lenon, G., Holbom, B., Locke, I.C., Thompson, S. and Keshavarz, T. 2006. Biological activity of industrial wood and bark waste from Pinus nigra. in: Actual problems of creation of new medicinal preparations of natural origin: the 10th international congress PHYTOPHARM 2006, St.-Petersburg, June 27-30, 2006: proceedings of congress St Petersburg, Russia PHYTOPHARM. pp. 401-403

In vitro and in vivo induction of heme oxygenase 1 in mouse macrophages following melanocortin receptor activation
Lam, C.W., Getting, S.J. and Perretti, M. 2005. In vitro and in vivo induction of heme oxygenase 1 in mouse macrophages following melanocortin receptor activation. Journal of Immunology. 174 (4), pp. 2297-2304.

Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery into MEG-01 megakaryocytes
Shah, C.M., Walters, S.E., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2005. Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery into MEG-01 megakaryocytes. Ireland-UK Platelet Conference 2005. Dublin, Ireland 04-06 Sep 2005

Evidence for a neuroprotective role of the CRH-like peptide, urocortin, in the 6-hydroxydopamine treated rat
Biggs, C.S., Locke, I.C., Knight, R.A., Chowdrey, H.S. and Whitton, P.S. 2005. Evidence for a neuroprotective role of the CRH-like peptide, urocortin, in the 6-hydroxydopamine treated rat. 18th National Meeting of the British Neuroscience Association. Brighton, UK 03-06 Apr 2005

Urocortin attenuates key indicators of nigrostriatal pathway destruction in a rat hemiparkinsonian model
Biggs, C.S., Abuirmeileh, A., Locke, I.C., Knight, R.A., Chowdrey, H.S. and Whitton, P.S. 2005. Urocortin attenuates key indicators of nigrostriatal pathway destruction in a rat hemiparkinsonian model. Proceedings of the British Pharmacological Society. 3 (4).

MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct
Getting, S.J., Di Filippo, C., Christian, H.C., Lam, C.W., Rossi, F., D'Amico, M. and Perretti, M. 2004. MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct. Journal of Leukocyte Biology. 76 (4), pp. 845-853.

Inhibitory effects of TSG-6 Link module on leukocyte-endothelial cell interactions in vitro and in vivo
Cao, T.V., La, M., Getting, S.J. and Day, A.J. 2004. Inhibitory effects of TSG-6 Link module on leukocyte-endothelial cell interactions in vitro and in vivo. Microcirculation. 11 (7), pp. 615-624.

Functional characteristics of the streptococcal deoxyribonuclease 'streptodornase', a protein with DNase activity present in the medicament Varidase
Locke, I.C. and Carpenter, B.G. 2004. Functional characteristics of the streptococcal deoxyribonuclease 'streptodornase', a protein with DNase activity present in the medicament Varidase. Enzyme and Microbial Technology. 35 (1), pp. 67-73.

Investigation into the potential anti-inflammatory effects of endothelin antagonists in a murine model of experimental monosodium urate peritonitis
Getting, S.J., Di Filippo, C., Lam, C.W., Rossi, F. and D'Amico, M. 2004. Investigation into the potential anti-inflammatory effects of endothelin antagonists in a murine model of experimental monosodium urate peritonitis. Journal of Pharmacology and Experimental Therapeutics. 310 (1), pp. 90-97.

Cytotoxicity of lavender oil and its major components to human skin cells
Prashar, A., Locke, I.C. and Evans, C.S. 2004. Cytotoxicity of lavender oil and its major components to human skin cells. Cell Proliferation. 37 (3), pp. 221-229.

Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis
Yang, Y.H., Morand, E.F., Getting, S.J. and Paul-Clark, M. 2004. Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis. Arthritis & Rheumatism. 50 (3), pp. 976-984.

The annexin 1-/- mouse: phenotypic studies
Wells, D., Wells, K., Liu, K., Hannon, R., Croxtall, J.D., Damazo, A.S., Oliani, S.M., Getting, S.J., Parente, L., Paul-Clark, M., Yona, S., Gavins, F.N.E., Martin, J., Christian, H.C., Cover, P.O., John, C.D., Solito, E., Morris, J.F., Perretti, M., Buckingham, J.C. and Flower, R.J. 2004. The annexin 1-/- mouse: phenotypic studies. Annexins. 1 (2), pp. 109-120.

Cell surface thiol modification by GSNO: a mechanism of nitric oxide delivery?
Shah, C.M., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2004. Cell surface thiol modification by GSNO: a mechanism of nitric oxide delivery? 5th UK Nitric Oxide Forum. Edinburgh, UK 12/2004

Protein disulphide isomerase is involved in the delivery of NO from S-nitrosoglutathione into megakaryocytes
Shah, C.M., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2004. Protein disulphide isomerase is involved in the delivery of NO from S-nitrosoglutathione into megakaryocytes. 3rd International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide: 4th Anuual Scientific Meeting of the Nitric Oxide Society of Japan. Nara, Japan 24-28 May 2004

Protein disulphide isomerase is involved in the delivery of NO from S-nitrosoglutathione into megakaryocytes
Shah, C.M., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2004. Protein disulphide isomerase is involved in the delivery of NO from S-nitrosoglutathione into megakaryocytes. Japan-UK Platelet Conference. Oxford, UK September 2004

Establishment and analysis of 3-D collagen cultures of C-20/A4 chondrocytes
Petsa, A., Chowdrey, H.S., Knight, R.A., Afoke, A. and Locke, I.C. 2004. Establishment and analysis of 3-D collagen cultures of C-20/A4 chondrocytes. OARSI 2004 World Congress on Osteoarthritis. Chicago USA 12/2004

Activation of melanocortin receptors induces cAMP-dependent hemeoxygenase-1 expression in murine macrophages
Lam, C.W., Getting, S.J. and Perretti, M. 2004. Activation of melanocortin receptors induces cAMP-dependent hemeoxygenase-1 expression in murine macrophages. pA2 Online. Winter 2004 Meeting: Proceedings of the British Pharmacological Society.

Melanocortin receptor type 3 as a potential target for anti-inflammatory therapy
Lam, C.W. and Getting, S.J. 2004. Melanocortin receptor type 3 as a potential target for anti-inflammatory therapy. Current Drug Targets. Inflammation & Allergy. 3 (3), pp. 311-315.

A CRH family peptide protects a human chondrocyte cell line against apoptosis
Intekhab-Alam, N.Y., Chowdrey, H.S., Knight, R.A., Locke, I.C. and Intekhab Alam, N.Y. 2004. A CRH family peptide protects a human chondrocyte cell line against apoptosis. OARSI 2004 World Congress on Osteoarthritis. Chicago USA 12/2004

Rapid S-nitrosothiol metabolism by platelets and megakaryocytes
Shah, C.M., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2003. Rapid S-nitrosothiol metabolism by platelets and megakaryocytes. Biochemical Society Transactions. 31 (6), pp. 1450-1452.

Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides
Getting, S.J., Schiöth, H.B. and Perretti, M. 2003. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. Journal of Pharmacology and Experimental Therapeutics. 306 (2), pp. 631-637.

Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory actions of melanocortin peptides: studies in the recessive yellow (e/e) mouse suggest an important role for melanocortin 3 receptor
Getting, S.J., Christian, H.C., Lam, C.W., Gavins, F.N.E., Flower, R.J., Schiöth, H.B. and Perretti, M. 2003. Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory actions of melanocortin peptides: studies in the recessive yellow (e/e) mouse suggest an important role for melanocortin 3 receptor. Journal of Immunology. 170 (6), pp. 3323-3330.

Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse
Hannon, R., Croxtall, J.D., Getting, S.J., Roviezzo, F., Yona, S., Paul-Clark, M., Gavins, F.N.E., Perretti, M., Morris, J.F., Buckingham, J.C. and Flower, R.J. 2003. Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse. FASEB Journal. 17 (2), pp. 253-255.

Role of protein disulphide isomerase in NO delivery from S-nitrosothiols into megakaryocytes
Shah, C.M., Locke, I.C., Chowdrey, H.S. and Gordge, M.P. 2003. Role of protein disulphide isomerase in NO delivery from S-nitrosothiols into megakaryocytes. 4th UK Nitric Oxide Forum. University of Nottingham, UK December 2003

The behaviour of C-20/A4 chondrocytes in 3-D collagen gel cultures
Petsa, A., Afoke, A., Chowdrey, H.S., Knight, R.A., Harris, A. and Locke, I.C. 2003. The behaviour of C-20/A4 chondrocytes in 3-D collagen gel cultures. OARSI 2003 World Congress on Osteoarthritis. Berlin, Germany October 2003

Migration of specific leukocyte subsets in response to cytokine or chemokine application in vivo
Perretti, M. and Getting, S.J. 2003. Migration of specific leukocyte subsets in response to cytokine or chemokine application in vivo. Methods in Molecular Biology. 225, pp. 139-146.

Migration of specific leukocyte sub-sets in response to cytokine or chemokine application in vivo
Perretti, M. and Getting, S.J. 2003. Migration of specific leukocyte sub-sets in response to cytokine or chemokine application in vivo. in: Winyard, P.G. and Willoughby, D.A. (ed.) Inflammation Protocols Totowa, NJ Humana Press. pp. 139-146

The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner
Getting, S.J., Mahoney, D.J., Cao, T.V., Rugg, M.S., Fries, E., Milner, C.M., Perretti, M. and Day, A.J. 2002. The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner. Journal of Biological Chemistry. 277 (52), pp. 51068-51076.

The annexin-1 knockout mouse: what it tells us about the inflammatory response
Roviezzo, F., Getting, S.J., Paul-Clark, M., Yona, S., Gavins, F.N.E., Perretti, M., Hannon, R., Croxtall, J.D., Buckingham, J.C. and Flower, R.J. 2002. The annexin-1 knockout mouse: what it tells us about the inflammatory response. Journal of Physiology and Pharmacology. 53 (4, part 1), pp. 541 -553.

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor
Perretti, M., Chiang, N., La, M., Fierro, I.M., Marullo, S., Getting, S.J., Solito, E. and Serhan, C.N. 2002. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nature Medicine. 8 (11), pp. 1296-1302.

Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis
Getting, S.J., Christian, H.C., Flower, R.J. and Perretti, M. 2002. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis & Rheumatism. 46 (10), pp. 2765-2775.

Melanocortin peptides and their receptors: new targets for anti-inflammatory therapy
Getting, S.J. 2002. Melanocortin peptides and their receptors: new targets for anti-inflammatory therapy. Trends in Pharmacological Sciences. 23 (10), pp. 447-449.

Ion-dependency of the streptococcal deoxyribonuclease "streptodornase", an active constituent of the medicament Varidase
Locke, I.C. and Carpenter, B.G. 2002. Ion-dependency of the streptococcal deoxyribonuclease "streptodornase", an active constituent of the medicament Varidase. Enzyme and Microbial Technology. 31 (4), pp. 482-489.

A novel control mechanism based on GDNF modulation of somatostatin release from sensory neurones
Malcangio, M., Getting, S.J., Grist, J., Cunningham, J.R., Bradbury, E.J., Issa, P.C., Lever, I.J., Pezet, S. and Perretti, M. 2002. A novel control mechanism based on GDNF modulation of somatostatin release from sensory neurones. FASEB Journal. 16 (7), pp. 730-732.

Effect of essential oils and their components on cell
Prashar, A., Veness, R., Locke, I.C. and Evans, C.S. 2002. Effect of essential oils and their components on cell. Future Trends in Phytochemistry. Gargnano, Italy

Characterization of CXC and CC chemokine expression in a murine model of chronic granuloma
Carollo, M., Getting, S.J., Delaney, S., Christie, M.I. and Perretti, M. 2002. Characterization of CXC and CC chemokine expression in a murine model of chronic granuloma. Inflammation Research. 51 (2), pp. 110-111.

Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics
Perretti, M., Getting, S.J., Solito, E., Murphy, P.M. and Gao, J.L. 2001. Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. American Journal of Pathology. 158 (6), pp. 1969-1973.

Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase
Mabley, J.G., Jagtap, P., Perretti, M., Getting, S.J., Salzman, A.L., Virag, L., Szabo, E., Soriano, F.G., Liaudet, L., Hasko, G., Marton, A., Southan, G.J., Abdelkarim, G.E. and Szabo, C. 2001. Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase. Inflammation Research. 50 (11), pp. 561-569.

Arthritic diseases: melanocortin type 3 receptor agonists as potential therapeutics
Getting, S.J. and Perretti, M. 2001. Arthritic diseases: melanocortin type 3 receptor agonists as potential therapeutics. Current opinion in investigational drugs. 2 (8), pp. 1064-1069.

Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties
Getting, S.J., Allcock, G.H., Flower, R.J. and Perretti, M. 2001. Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties. Journal of Leukocyte Biology. 69 (1), pp. 98-104.

Varidase: the science behind the medicament
Rutter, P.M., Carpenter, B.G., Hill, S.S. and Locke, I.C. 2000. Varidase: the science behind the medicament. Journal of Wound Care. 9 (5), pp. 223-226.

MC3-R as a novel target for anti-inflammatory therapy
Getting, S.J. and Perretti, M. 2000. MC3-R as a novel target for anti-inflammatory therapy. Drug News & Perspectives. 13 (1), pp. 19-27.

POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation
Getting, S.J., Gibbs, L., Clark, A.J.L., Flower, R.J. and Perretti, M. 1999. POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation. Journal of Immunology. 162 (12), pp. 7446-7453.

A comparison of the characteristics of circulating anti-myeloperoxidase antibodies in vasculitis with those in non-vasculitic conditions
Locke, I.C., Leaker, B. and Cambridge, G. 1999. A comparison of the characteristics of circulating anti-myeloperoxidase antibodies in vasculitis with those in non-vasculitic conditions. Clinical and Experimental Immunology. 115 (2), pp. 369-376.

Compounds for use in the treatment of inflammation
Flower, R.J., Getting, S.J. and Perretti, M. 1998. Compounds for use in the treatment of inflammation.

A comparison of the variable region genes of two human monoclonal antibodies to myeloperoxidase
Locke, I.C., Rahman, M.A.A. and Cambridge, G. 1998. A comparison of the variable region genes of two human monoclonal antibodies to myeloperoxidase. British Society for Immunology 6th Annual Meeting. Harrogate, UK 12/1998

Adjacent proline residues in the inhibitory domain of the Oct-2 transcription factor play distinct functional roles
Liu, Y.Z., Lee, I.K., Locke, I.C., Dawson, S. and Latchman, D. 1998. Adjacent proline residues in the inhibitory domain of the Oct-2 transcription factor play distinct functional roles. Nucleic Acids Research. 26 (10), pp. 2464-2472.

Purification of a streptococcal deoxyribonuclease by affinity chromatography based on a DNA-cellulose matrix
Locke, I.C., Cox, S.F. and Carpenter, B.G. 1997. Purification of a streptococcal deoxyribonuclease by affinity chromatography based on a DNA-cellulose matrix. Journal of Chromatography A. 788 (1-2), pp. 75-80.

Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts anti-inflammatory effects
Szabo, C., Lim, L.H.K., Cuzzocrea, S., Getting, S.J., Zingarelli, B., Flower, R.J., Salzman, A.L. and Perretti, M. 1997. Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts anti-inflammatory effects. Journal of experimental medicine. 186 (7), pp. 1041-1049.

Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins
Getting, S.J., Flower, R.J., Parente, L., de Medicis, R., Lussier, A., Woliztky, B.A., Martins, M.A. and Perretti, M. 1997. Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins. Journal of Pharmacology and Experimental Therapeutics. 283 (1), pp. 123-130.

Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1
Getting, S.J., Flower, R.J. and Perretti, M. 1997. Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1. British Journal of Pharmacology. 120 (6), pp. 1075-1082.

Sub-acute treatment of rats with dexamethasone reduces ICAM-1 levels on circulating monocytes
Tailor, A., Das, A.M., Getting, S.J., Flower, R.J. and Perretti, M. 1997. Sub-acute treatment of rats with dexamethasone reduces ICAM-1 levels on circulating monocytes. Biochemical and Biophysical Research Communications. 231 (3), pp. 675-678.

Autoantibodies to myeloperoxidase in systemic sclerosis
Locke, I.C., Worral, J.G., Leaker, B., Black, C.M. and Cambridge, G. 1997. Autoantibodies to myeloperoxidase in systemic sclerosis. Journal of Rheumatology. 24 (1), pp. 86-89.

Biphasic modulation of GABA release by nitric oxide in the hippocampus of freely moving rats in vivo
Getting, S.J., Segieth, J., Ahmad, S., Biggs, C.S. and Whitton, P.S. 1996. Biphasic modulation of GABA release by nitric oxide in the hippocampus of freely moving rats in vivo. Brain Research. 717 (1-2), pp. 196-199.

Characteristics of antibodies to myeloperoxidase in vasculitic and non-vasculitic conditions
Locke, I.C., Leaker, B. and Cambridge, G. 1996. Characteristics of antibodies to myeloperoxidase in vasculitic and non-vasculitic conditions. American College of Rheumatology 60th National Scientific Meeting. Orlando, USA 10/1996

Characteristics of anti-myeloperoxidase autoantibodies in vasculitis and other conditions
Locke, I.C., Leaker, B. and Cambridge, G. 1996. Characteristics of anti-myeloperoxidase autoantibodies in vasculitis and other conditions. American Society of Nephrology 29th Annual Meeting. New Orleans, USA 11/1996

Autoantibodies to neutrophil granule proteins: pathogenic potential in vasculitis?
Locke, I.C. and Cambridge, G. 1996. Autoantibodies to neutrophil granule proteins: pathogenic potential in vasculitis? British Journal of Biomedical Science. 53 (4), pp. 302-316.

A human monoclonal anti-myeloperoxidase antibody can prime human neutrophils in vitro
Cambridge, G., Leaker, B., Locke, I.C., Noronha-Dutra, A. and Epperlein, M. 1996. A human monoclonal anti-myeloperoxidase antibody can prime human neutrophils in vitro. American Society of Nephrology 29th Annual Meeting. New Orleans, USA 11/1996

Nitric oxide regulates excitatory amino acid release in a biphasic manner in freely moving rats
Segieth, J., Getting, S.J., Biggs, C.S. and Whitton, P.S. 1995. Nitric oxide regulates excitatory amino acid release in a biphasic manner in freely moving rats. Neuroscience Letters. 200 (2), pp. 101-104.

Effect of nitric oxide on basal and NMDA-evoked release of glutamate and aspartate release in vivo
Segieth-Beever, J., Getting, S.J., Biggs, C.S. and Whitton, P.S. 1995. Effect of nitric oxide on basal and NMDA-evoked release of glutamate and aspartate release in vivo. Wiley.

Autoantibodies to myeloperoxidase in systemic sclerosis
Worral, J.G., Locke, I.C., Leaker, B., Black, C.M. and Cambridge, G. 1995. Autoantibodies to myeloperoxidase in systemic sclerosis. British Society for Rheumatology Heberden Round 1995. Keele University, UK 9/1995

Automated analysis of the deoxyribonuclease active constituents of the medicament Varidase ®
Locke, I.C., Ramsay, M.P., Hill, S.S. and Carpenter, B.G. 1993. Automated analysis of the deoxyribonuclease active constituents of the medicament Varidase ®. The Journal of Automatic Chemistry. 15, pp. 65-70.

Automated analysis of the deoxyribonuclease active constituents of the medicament Varidase ®
Locke, I.C., Ramsey, M.P., Hill, S.S. and Carpenter, B.G. 1992. Automated analysis of the deoxyribonuclease active constituents of the medicament Varidase ®. IMLS XX Triennial Conference. Liverpool, UK 9/1992

Purification of the seed lectin from Dolichos biflorus by chromatofocusing
Rogers, D.J., Locke, I.C., Gibbs, R. and Carpenter, B.G. 1990. Purification of the seed lectin from Dolichos biflorus by chromatofocusing. 12th International Lectin Conference. University of Davis, USA 9/1990

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