Oxidative Stress-Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo
Oxidative Stress-Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo
复制标题
氧化应激诱导黑素细胞释放 HMGB1：白癜风皮肤炎症的旁分泌机制
DOI：
10.1016/j.jid.2019.03.1148
复制
发表时间：
2019-10-01
影响因子：
6.5
通讯作者：
Li, Chunying
中科院分区：
文献类型：
--
作者：
Cui, Tingting;Zhang, Weigang;Li, Chunying
白癜风是一种由表皮黑素细胞破坏引起的皮肤色素脱失性疾病。氧化应激引发的自身反应性CD8+细胞毒性T细胞的产生和皮肤浸润在白癜风中发挥着关键作用。高迁移率族蛋白B1（HMGB1）是一种经典的损伤相关分子模式分子，在炎症反应中具有强烈的促炎作用。此前有研究报道HMGB1在白癜风皮损中表达增强，但HMGB1在白癜风皮肤炎症中的作用仍不清楚。在本研究中，我们最初发现HMGB1是从白癜风病灶周围皮肤的黑素细胞核中释放出来的。此外，培养的正常人类黑素细胞在过氧化氢处理下可以释放 HMGB1。此外，HMGB1 通过与晚期糖基化终产物受体结合并激活 NF-κ B 和细胞外信号调节激酶信号通路，促进角质形成细胞分泌 CXCL16 和 IL-8。随后，HMGB1通过增加角质形成细胞中CXCL16的释放，导致白癜风患者的CD8+T细胞迁移形成趋化性。此外，HMGB1 还能促进白癜风患者树突状细胞的成熟。总而言之，我们的研究表明，黑素细胞释放的 HMGB1 有助于白癜风氧化应激诱导的自身免疫的形成。
Vitiligo is a cutaneous depigmentation disorder caused by the destruction of epidermal melanocytes. The generation and the skin infiltration of autoreactive CD8(+) cytotoxic T cells triggered by oxidative stress play a critical role in vitiligo. High-mobility group protein B1 (HMGB1) is a classic damage-associated molecular pattern molecule with strong proinflammatory effects in inflammatory reactions. A previous study reported an enhanced expression of HMGB1 in vitiligo lesions, but the role of HMGB1 in cutaneous inflammation of vitiligo is still unknown. In the present study, we initially found that HMGB1 was released from the nucleus of melanocytes in vitiligo perilesional skin. Furthermore, cultured normal human melanocytes could release HMGB1 under treatment with hydrogen peroxide. Moreover, HMGB1 facilitated the secretion of CXCL16 and IL-8 from keratinocytes by binding to the receptor for advanced glycation end products and activating NF-kappa B and extracellular signal-regulated kinase signaling pathways. Subsequently, HMGB1 led to the formation of chemotaxis for the migration of CD8(+) T cells from patients with vitiligo by increasing the release of CXCL16 from keratinocytes. Additionally, HMGB1 promoted the maturation of dendritic cells from patients with vitiligo. Altogether, our study demonstrates that HMGB1 released from melanocytes contributes to the formation of oxidative stress-induced autoimmunity in vitiligo.