Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress.

Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress.
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DOI:
10.1111/pcmr.12208
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发表时间:
2014-03
影响因子:
4.3
通讯作者:
Le Poole IC
Le Poole IC
中科院分区:
医学3区
文献类型:
--
作者:
Mosenson JA;Flood K;Klarquist J;Eby JM;Koshoffer A;Boissy RE;Overbeck A;Tung RC;Le Poole IC

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来自应激细胞的诱导型HSP70(HSP70i)分子伴侣肽,保护它们免于凋亡。在细胞外释放后,HSP 70 i起到佐剂作用,增强对结合肽的免疫应答。我们质疑HSP70 i是否能不同程度地保护对照组和白癜风患者的黑素细胞免受应激和随后的免疫反应的影响。我们比较了皮肤样本中HSP70 i的表达,评估了暴露于漂白酚的原发性白癜风和对照黑素细胞的活力,并测量了分泌的HSP70 i。我们通过细胞分级分离、免疫印迹、电子显微镜和共聚焦显微镜来确定HSP70 i是否运输到黑素体以接触免疫原性蛋白。白癜风和对照黑素细胞的活力在压力下同样受到影响。然而,白癜风黑素细胞分泌增加量的HSP70 i,以响应MBEH,证实了患者皮肤中的异常HSP70 i表达。细胞内HSP 70 i与黑素体共定位,并且在白癜风黑素细胞中对MBEH的反应更是如此。因此,尽管任一药剂对黑素细胞具有细胞毒性,但MBEH优先诱导对黑素细胞的免疫应答。
Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes.
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