Interferon-? induces senescence in normal human melanocytes.

ABSTRACT: BACKGROUND: Interferon-? (IFN-?) plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-? on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear. OBJECTIVE: To investigate the effects of IFN-? on viability and cellular functions of melanocytes. METHODS: Primary human melanocytes were treated with IFN-?. Cell viability, apoptosis, cell cycle melanin content and intracellular reactive oxygen species (ROS) level were measured. mRNA expression was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock protein 70 (HSP-70) was monitored by ELISA. ?-galactosidase staining was utilized to evaluate melanocyte senescence. RESULTS: Persistent IFN-? treatment induced viability loss, apoptosis, cell cycle arrest and senescence in melanocytes. Melanocyte senescence was characterized as the changes in pigmentation and morphology, as well as the increase of ?-galactosidase activity. Increase of p21Cip1/Waf1 protein was evident in melanocytes after IFN-? treatment. IFN-? induction of senescence was attenuated by siRNAs against p21, Janus kinase 2 (JAK2) or signal transducer and activator of transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin-?. IFN-? treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited IFN-? induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-? treatment, which was largely inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed in senescent melanocytes. CONCLUSION: IFN-? can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu.

SUBMITTER: Wang S 

PROVIDER: S-EPMC3969336 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature