title: The Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional Responses through IRAK-M in Normal Human Keratinocytes.
abstract: 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.
authors: Department of Dermatology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, United States of America; Department of Biotechnology, Chosun University School of Medicine, Gwangju, South Korea.
authors: Sunhyo
authors: S
authors: Ryu
authors: Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arizona, United States of America.
authors: Andrew
authors: A
authors: Johnson
authors: Department of Biotechnology, Chosun University School of Medicine, Gwangju, South Korea.
authors: Yoonkyung
authors: Y
authors: Park
authors: Department of Dermatology, Chung-Ang University School of Medicine, Seoul, South Korea.
authors: Beomjoon
authors: B
authors: Kim
authors: Department of Dermatology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors: David
authors: D
authors: Norris
authors: Department of Dermatology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, United States of America; Division of Dermatology, Denver Health Medical Center, Denver, Colorado, United States of America.
authors: Cheryl A
authors: CA
authors: Armstrong
authors: Department of Dermatology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors: Peter I
authors: PI
authors: Song
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013211:Staphylococcus aureus / Q000378:metabolism; D013682:Teichoic Acids / Q000096:biosynthesis / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid; D000521:alpha-MSH; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases