The Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional Responses through IRAK-M in Normal Human Keratinocytes.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Interleukin-1 Receptor-Associated Kinases/*metabolism ; Keratinocytes/*drug effects ; Keratinocytes/*metabolism ; Toll-Like Receptor 2/*metabolism ; alpha-MSH/*pharmacology; Active Transport, Cell Nucleus/drug effects ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Gene Expression Regulation, Enzymologic/drug effects ; Gene Silencing ; Humans ; Interleukin-1 Receptor-Associated Kinases/deficiency ; Interleukin-1 Receptor-Associated Kinases/genetics ; Interleukin-8/biosynthesis ; Interleukin-8/genetics ; Keratinocytes/cytology ; Keratinocytes/microbiology ; Lipopolysaccharides/biosynthesis ; Lipopolysaccharides/pharmacology ; NF-kappa B/metabolism ; RNA, Small Interfering/genetics ; Staphylococcus aureus/metabolism ; Teichoic Acids/biosynthesis ; Teichoic Acids/pharmacology ; Toll-Like Receptor 2/genetics

Alpha-melanocyte stimulating hormone (α-MSH) is a highly conserved 13-aa neuropeptide derived from pro-opiomelanocortin by post-translational processing, which has been reported to exhibit potent anti-inflammatory activity and a wide range of immunosuppressive activities in the skin. However, the regulatory effect of α-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of α-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs). α-MSH pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of both TLR2 and IL-8 as well as NF-κB nuclear translocation in HK cells. The inhibitory effect of α-MSH was blocked by agouti signaling protein (ASP), an α-MSH receptor-1 antagonist. To investigate the mechanism of this response in more detail, siRNA of IRAK-M, a negative regulator of TLR signaling, was utilized in these studies. The α-MSH suppressive effect on IL-8 production and NF-κB transactivation was inhibited by IRAK-M siRNA transfection in HK cells. These results indicate that α-MSH is capable of suppressing keratinocyte TLR2-mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating another novel immunomodulatory activity of α-MSH in normal human keratinocytes.

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R01 AR052643 United States AR NIAMS NIH HHS

0 (Interleukin-8)
0 (Lipopolysaccharides)
0 (NF-kappa B)
0 (RNA, Small Interfering)
0 (TLR2 protein, human)
0 (Teichoic Acids)
0 (Toll-Like Receptor 2)
56411-57-5 (lipoteichoic acid)
581-05-5 (alpha-MSH)
EC 2.7.11.1 (IRAK3 protein, human)
EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)

Date Created: 20150827 Date Completed: 20160516 Latest Revision: 20181113

20221213

PMC4550463

10.1371/journal.pone.0136887

26309029