title: Differential responses of normal human melanocytes to intra- and extracellular dsRNA.
abstract: Viral factor has been implicated in the etiopathogenesis of vitiligo. To elucidate the effects of viral double-stranded RNA (dsRNA) on melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were treated with synthetic viral dsRNA analog poly(I:C). The results demonstrated that poly(I:C)-triggered apoptosis when transfected into melanocytes, while extracellular poly(I:C) did not have that effect. Intracellular poly(I:C)-induced melanocyte death was decreased by RIG-I or MDA5 siRNA, but not by TLR3 siRNA. Both intracellular and extracellular poly(I:C) induced the expression of IFNB, TNF, IL6, and IL8. However, extracellular poly(I:C) demonstrated a much weaker induction capacity of cytokine genes than intracellular poly(I:C). Further analysis revealed that phosphorylation of TBK1, IRF3, IRF7, and TAK1 was differentially induced by intra- or extracellular poly(I:C). NFκB inhibitor Bay 11-7082 decreased the induction of all the cytokines by poly(I:C), suggesting the ubiquitous role of NFκB in the process. Poly(I:C) treatment also induced the phosphorylation of p38 and JNK in melanocytes. Both JNK and p38 inhibitors showed suppression on the cytokine induction by intra- or extracellular poly(I:C). However, only the JNK inhibitor decreased the intracellular poly(I:C)-induced melanocyte death. Taken together, this study provides the possible mechanism of viral factor in the pathogenesis of vitiligo.
authors: Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China.
authors: Suiquan
authors: S
authors: Wang
authors: Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China.
authors: Dongyin
authors: D
authors: Liu
authors: Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China.
authors: Rong
authors: R
authors: Jin
authors: Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China.
authors: Yiping
authors: Y
authors: Zhu
authors: Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, China.
authors: Aie
authors: A
authors: Xu
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008544:Melanocytes / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012367:RNA, Viral / Q000494:pharmacology; D011971:Receptors, Immunologic; D015533:Transcriptional Activation / Q000187:drug effects; D014820:Vitiligo / Q000821:virology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D048051:p38 Mitogen-Activated Protein Kinases; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C