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

Kim,Young Il; Park,Seung-Won; Kang,In Jung; Shin,Min  Kyung; Lee,Mu-Hyoung

doi:10.3892/ijmm.2015.2308

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

Authors:
- Young Il Kim
- Seung-Won Park
- In Jung Kang
- Min Kyung Shin
- Mu-Hyoung Lee
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Affiliations: Medical Science Research Institute, Kyung Hee University Medical Center and East-West Medical Research Institute, Kyung Hee University, Seoul 130-872, Republic of Korea, Department of Biotechnology, Catholic University of Daegu, Daegu 712-702, Republic of Korea, Department of Dermatology, College of Medicine, Kyung Hee University, Seoul 130-872, Republic of Korea
Published online on: August 10, 2015 https://doi.org/10.3892/ijmm.2015.2308
Pages: 1165-1172

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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.

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