Cytosolic ds DNA triggers apoptosis and pro‐inflammatory cytokine production in normal human melanocytes

• Published in: Experimental dermatology Vol. 24; no. 4; pp. 298 - 300
• Main Authors: Wang, Suiquan, Liu, Dongyin, Ning, Weixuan, Xu, Aie
• Format: Journal Article
• Language: English
• Published: 01.04.2015
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.12621

Abstract Considerable evidence implicates that viral infection might be a participant factor in the pathogenesis of vitiligo. However, it is still unclear how viral infection leads to the melanocyte destruction. To elucidate the effects of viral ds DNA on the viability and cytokine synthesis of normal human melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were transfected with poly( dA : dT ). The results demonstrated that poly( dA : dT ) triggered apoptosis instead of pyroptosis in melanocytes. Knocking down AIM 2 or RIG ‐I by RNA interference partially reduced the poly( dA : dT )‐induced LDH release, suggesting the involvement of both nucleic acid sensors in the process of melanocyte death. Poly( dA : dT ) induced the expression of pro‐inflammatory cytokine genes including IFN ‐β, TNF ‐α, IL ‐6 and IL ‐8 as well, whereas the pro‐inflammatory cytokine production was suppressed by RIG ‐I si RNA , but not by AIM 2 si RNA . Poly( dA : dT ) treatment increased the phosphorylation of p38 and JNK and NF κB. Accordingly, NF κB inhibitor Bay 11‐7082 and JNK inhibitor SP 600125 blocked the induction of the cytokine genes except IFN ‐β. The production of IL 6 and IL 8 was also suppressed by p38 inhibitor SB 203580. On the contrary, the Poly( dA : dT )‐induced melanocyte death was only decreased by SP 600125. This study provides the possible mechanism of melanocyte destruction and immuno‐stimulation in vitiligo by innate immune response following viral infection.