| Double-stranded RNA induces melanocyte death via activation of Toll-like receptor 3. | |
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MedLine Citation:
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PMID: 21255093 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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As cutaneous pigment-producing cells, melanocytes can become targets of primary and secondary immune response as can be seen in diseases like vitiligo and Vogt-Koyanagi-Harada (VKH) syndrome. Viral infections have previously been implicated as a possible precipitating factor in the destruction of melanocytes in these disorders. During viral replication, double-stranded RNA (dsRNA) is produced as an intermediate metabolite, which induces antiviral and inflammatory responses through Toll-like receptor 3 (TLR3) in cells of innate immune system. The functional responses of melanocytes to dsRNA, however, remain unclear. Herein, we demonstrated that human melanocytes expressed TLR3 at a constitutive and inducible level. Stimulation with poly(I:C), a synthetic dsRNA analogue, triggered apoptosis of melanocytes. The apoptosis-inducing effect was shown by RNA interference to be largely dependent on TLR3, but occurred independently of NF-κB activation since treatment with specific NF-κB inhibitor Bay 11-7082 failed to prevent the process. In contrast, IFN-β neutralizing Ab blocked the apoptosis-inducing effect of dsRNA, indicating the involvement of IFN-β autocrine signalling. Furthermore, studies on the intracellular signal transduction pathways revealed that dsRNA induces the activation of p38, ERK1/2 and JNK1/2 in melanocytes. Using specific inhibitors, we demonstrated that activation of p38 and ERK1/2 controlled both IFN-β secretion and IFN-β mediated cell death. Taken together, these data suggest that viral dsRNA stimulates TLR3 in human melanocytes and triggers the cellular apoptosis through autocrine of IFN-β. |
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Authors:
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Ning Yu; Shujie Zhang; Tao Sun; Kefei Kang; Ming Guan; Leihong Xiang |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Experimental dermatology Volume: 20 ISSN: 1600-0625 ISO Abbreviation: Exp. Dermatol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9301549 Medline TA: Exp Dermatol Country: Denmark |
Other Details:
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Languages: eng Pagination: 134-9 Citation Subset: IM |
Copyright Information:
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© 2011 John Wiley & Sons A/S. |
Affiliation:
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Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, China Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, China Central Laboratory, Huashan Hospital, Fudan University, Shanghai, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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