Manna, S.K. and Sarkar, A. and Sreenivasan, Y. (2006) α-melanocyte-stimulating hormone down-regulates CXC receptors through activation of neutrophil elastase. European Journal of Immunology, 36 (3). pp. 754-769. ISSN 0014-2980

Text Eur J Immunol 36 p754.pdf Restricted to Repository staff only Download (735Kb) | Request a copy

Abstract

Considering the role of interleukin-8 (IL-8) in a large number of acute and chronic inflammatory diseases, the regulation of IL-8-mediated biological responses is important. Alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide, inhibits most forms of inflammation by an unknown mechanism. In the present study, we have found that alpha-MSH interacts predominantly with melanocortin-1 receptors and inhibits several IL-8-induced biological responses in macrophages and neutrophils. It down-regulated receptors for IL-8 but not for TNF, IL-4, IL-13 or TNF-related apoptosis-inducing ligand (TRAIL) in neutrophils. It down-regulated CXCR type 1 and 2 but not mRNA levels. alpha-MSH did not inhibit IL-8 binding in purified cell membrane or affinity-purified CXCR. IL-8 or anti-CXCR Ab protected against alpha-MSH-mediated inhibition of IL-8 binding. The level of neutrophil elastase, a specific serine protease, but not cathepsin G or proteinase 3 increased in alpha-MSH-treated cells, and restoration of CXCR by specific neutrophil elastase or serine protease inhibitors indicates the involvement of elastase in alpha-MSH-induced down-regulation of CXCR. These studies suggest that alpha-MSH inhibits IL-8-mediated biological responses by down-regulating CXCR through induction of serine protease and that alpha-MSH acts as a potent immunomodulator in neutrophil-driven inflammatory distress.

Item Type:	Article
Depositing User:	Users 2 not found.
Date Deposited:	28 Jul 2015 11:21
Last Modified:	28 Jul 2015 11:21
URI:	http://cdfd.sciencecentral.in/id/eprint/306

Actions (login required)

View Item