title: Activin suppresses LPS-induced Toll-like receptor, cytokine and inducible nitric oxide synthase expression in normal human melanocytes by inhibiting NF-κB and MAPK pathway activation.
abstract: Activins are dimeric growth and differentiation factors that belong to the transforming growth factor (TGF)-β superfamily of structurally related signaling proteins. In the present study, we examined the mechanisms through which activin regulates the lipopolysaccharide (LPS)-induced transcription of Toll-like receptors (TLRs), cytokines and inducible nitric oxide synthase (iNOS) in human melanocytes, as well as the involvement of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling. Cell proliferation was analyzed by cell viability assay, mRNA expression was detected by RT-qPCR, and protein expression was measured by western blot analysis. LPS increased the mRNA expression of TLRs (TLR1-10) and cytokines [interleukin (IL)-1β, IL-6, IL-8 and TNF-α], as well as the mRNA and protein expression of iNOS. Activin decreased the LPS-induced TLR and cytokine mRNA expression, as well as the LPS-induced iNOS mRNA and protein expression. In addition, activin suppressed NF-κB p65 activation and blocked inhibitor of NF-κB (IκBα) degradation in LPS-stimulated melanocytes, and reduced LPS-induced p38 MAPK and MEK/ERK activation. On the whole, our results demonstrated that activin inhibited TLR and cytokine expression in LPS-activated normal human melanocytes and suppressed LPS-induced iNOS gene expression. Moreover, the anti-inflammatory effects of activin were shown to be mediated through the suppression of NF-κB and MAPK signaling, resulting in reduced TLR and iNOS expression, and in the inhibition of inflammatory cytokine expression.
authors.affiliation: Medical Science Research Institute, Kyung Hee University Medical Center and East-West Medical Research Institute, Kyung Hee University, Seoul 130-872, Republic of Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Catholic University of Daegu, Daegu 712-702, Republic of Korea.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Dermatology, College of Medicine, Kyung Hee University, Seoul 130-872, Republic of Korea.
authors.forename: In Jung
authors.initials: IJ
authors.lastname: Kang
authors.affiliation: Department of Dermatology, College of Medicine, Kyung Hee University, Seoul 130-872, Republic of Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Shin
authors.affiliation: Department of Dermatology, College of Medicine, Kyung Hee University, Seoul 130-872, Republic of Korea.
authors.forename: Mu-Hyoung
authors.initials: MH
authors.lastname: Lee
mesh_terms: D028341:Activins / Q000494:pharmacology*; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D028341:Activins; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II