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

ABSTRACT: Alpha-melanocyte stimulating hormone (?-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 ?-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of ?-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs). ?-MSH pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of both TLR2 and IL-8 as well as NF-?B nuclear translocation in HK cells. The inhibitory effect of ?-MSH was blocked by agouti signaling protein (ASP), an ?-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 ?-MSH suppressive effect on IL-8 production and NF-?B transactivation was inhibited by IRAK-M siRNA transfection in HK cells. These results indicate that ?-MSH is capable of suppressing keratinocyte TLR2-mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating another novel immunomodulatory activity of ?-MSH in normal human keratinocytes.

SUBMITTER: Ryu S 

PROVIDER: S-EPMC4550463 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature