Vol 9: Interferon- Induces Senescence in Normal Human Melanocytes.Reportar como inadecuado



 Vol 9: Interferon- Induces Senescence in Normal Human Melanocytes.


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This article is from PLoS ONE, volume 9.AbstractBackground: Interferon-γ IFN-γ plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-γ on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear. Objective: To investigate the effects of IFN-γ on viability and cellular functions of melanocytes. Methods: Primary human melanocytes were treated with IFN-γ. 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. β-galactosidase staining was utilized to evaluate melanocyte senescence. Results: Persistent IFN-γ 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 β-galactosidase activity. Increase of p21Cip1-Waf1 protein was evident in melanocytes after IFN-γ treatment. IFN-γ 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-α. IFN-γ treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine NAC effectively inhibited IFN-γ induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-γ 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-γ can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu.



Autor: Wang, Suiquan; Zhou, Miaoni; Lin, Fuquan; Liu, Dongyin; Hong, Weisong; Lu, Liangjun; Zhu, Yiping; Xu, Aie

Fuente: https://archive.org/







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