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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Dissection of the Anti-Inflammatory Effect of the Core and C-Terminal (KPV) α-Melanocyte-Stimulating Hormone Peptides

Stephen J. Getting, Helgi B. Schiöth and Mauro Perretti
Journal of Pharmacology and Experimental Therapeutics August 2003, 306 (2) 631-637; DOI: https://doi.org/10.1124/jpet.103.051623
Stephen J. Getting
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Helgi B. Schiöth
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Mauro Perretti
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Abstract

In this study, we analyzed the anti-inflammatory effects of α-melanocyte stimulating hormone (MSH)11–13 (KPV) in comparison with other MSH peptides in a model of crystal-induced peritonitis. Systemic treatment of mice with KPV, α-MSH, the core melanocortin peptide His-Phe-Arg-Trp, and the melanocontin receptor 3/4 agonist Ac-Nle4-c[Asp5,d-Phe7,Lys10]NH2 ACTH4-10 (MTII) but not the selective MC1-R agonist H-Ser-Ser-Ile-Ile-Ser-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (MS05) resulted in a significant reduction in accumulation of polymorphonuclear leukocyte in the peritoneal cavity. The antimigratory effect of KPV was not blocked by the MC3/4-R antagonist Ac-Nle4-c[Asp5,d-2Nal7,Lys10]NH2 ACTH4-10 (SHU9119). In vitro, macrophage activation, determined as release of KC and interleukin (IL)-1β was inhibited by α-MSH and MTII but not by KPV. Furthermore, macrophage activation by MTII led to an increase in cAMP accumulation, which was attenuated by SHU9119, whereas KPV failed to increase cAMP. The anti-inflammatory properties of KPV were also evident in IL-1β-induced peritonitis inflammation and in mice with a nonfunctional MC1-R (recessive yellow e/e mice). In conclusion, these data highlight that the C-terminal MSH peptide KPV exhibits an anti-inflammatory effect that is clearly different from that of the core MSH peptides. KPV is unlikely to mediate its effects through melanocortin receptors but is more likely to act through inhibition of IL-1β functions.

Footnotes

  • This work was supported by the Arthritis Research Campaign UK (Grant G0571). M.P. is a Senior Fellow of the Association pour la Recherche sur le Cancer, UK. H.S. was supported by the Swedish Research Council (VR, medicin) and Melacure Therapeutics AB.

  • DOI: 10.1124/jpet.103.051623.

  • ABBREVIATIONS: MSH, melanocyte stimulating hormone; ACTH, adrenocorticotropin; MC-R, melanocortin receptor; IL, interleukin; MØ, macrophage; MSU, monosodium urate; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay; PMN, polymorphonuclear leukocyte.

    • Received March 14, 2003.
    • Accepted May 9, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 306 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 306, Issue 2
1 Aug 2003
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Dissection of the Anti-Inflammatory Effect of the Core and C-Terminal (KPV) α-Melanocyte-Stimulating Hormone Peptides

Stephen J. Getting, Helgi B. Schiöth and Mauro Perretti
Journal of Pharmacology and Experimental Therapeutics August 1, 2003, 306 (2) 631-637; DOI: https://doi.org/10.1124/jpet.103.051623

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Dissection of the Anti-Inflammatory Effect of the Core and C-Terminal (KPV) α-Melanocyte-Stimulating Hormone Peptides

Stephen J. Getting, Helgi B. Schiöth and Mauro Perretti
Journal of Pharmacology and Experimental Therapeutics August 1, 2003, 306 (2) 631-637; DOI: https://doi.org/10.1124/jpet.103.051623
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