Activation of the HMGB1‑TLR4‑NF‑κB pathway may occur in patients with atopic eczema.

Activation of the HMGB1‑TLR4‑NF‑κB pathway may occur in patients with atopic eczema.
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特应性湿疹患者可能会激活 HMGB1-TLR4-NF-kappa B 通路

DOI:
10.3892/mmr.2017.6942
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发表时间:
2017-09
影响因子:
3.4
通讯作者:
Liu HB
Liu HB
中科院分区:
医学4区
文献类型:
--
作者:
Wang Y;Weng H;Song JF;Deng YH;Li S;Liu HB

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高迁移率族蛋白B1(HMGB 1)在多种病理状态中发挥重要作用。Toll样受体4(TLR 4)作为HMGB 1受体之一,通过激活核因子NF-κ-B(NF-κB)参与某些炎症性疾病的发生发展。然而,关于HMGB 1、TLR 4和NF-κB在人类炎症性皮肤病中的作用的研究较少。本研究探讨HMGB 1、TLR 4和NF-κB p65在银屑病和特应性湿疹(AE)中的表达分布及特点。此外,进行免疫组织化学分析以评估它们在正常皮肤、AE或银屑病患者中的表达和分布。斯皮尔曼相关分析用于预测它们的相关性。本研究发现,与正常皮肤和银屑病皮肤相比,AE皮肤上皮细胞核中p65的表达明显增加(P<0.01)。AE皮肤细胞外HMGB 1水平也明显高于正常皮肤和银屑病皮肤(P<0.01)。同时,AE皮肤上皮细胞膜上TLR 4的表达较银屑病皮肤明显增加(P<0.01)。AE患者皮肤细胞外HMGB 1水平与上皮细胞膜TLR 4(r=0.3856; P<0.05)和上皮细胞核p65(r=0.5894; P<0.01)呈正相关。提示HMGB 1-TLR 4-NF-κB信号通路在AE中被激活,可能是其发病机制之一,而在银屑病中未被激活。因此,HMGB 1、TLR 4和NF-κB p65有可能成为治疗包括AE在内的人类炎症性皮肤病的靶点。
High mobility group protein B1 (HMGB1) has been reported to serve important roles in various pathological conditions. Toll-like receptor 4 (TLR4), as one of the HMGB1 receptors, has been reported to be involved in the development of certain inflammatory diseases by activating nuclear factor NF-κ-B (NF-κB). However, there are few studies investigating the effects of HMGB1, TLR4 and NF-κB on human inflammatory dermatoses. In the present study, the distribution and characteristics of HMGB1, TLR4 and NF-κB p65 expression in psoriasis and atopic eczema (AE) were investigated. In addition, immunohistochemical analysis was performed to evaluate their expression and distribution in normal skin, and in patients with AE or psoriasis. Spearman's correlation analysis was used to predicate their relevancy. The present study identified that the p65 level in epithelial nuclei in AE skin was increased compared with normal and psoriasis skin (P<0.01). The level of extracellular HMGB1 in AE skin was also increased compared with normal and psoriasis skin (P<0.01). Meanwhile, TLR4 expression on the epithelial membranes of AE skin was increased compared with psoriasis skin (P<0.01). Furthermore, the level of extracellular HMGB1 was positively correlated with epithelial membrane TLR4 (r=0.3856; P<0.05) and epithelial nuclear p65 (r=0.5894; P<0.01) in AE skin. These results indicated that the HMGB1-TLR4-NF-κB signaling pathway is activated in AE and may account for its pathogenesis, but not in psoriasis. Therefore, HMGB1, TLR4 and NF-κB p65 have the potential to be targets for the treatment of human inflammatory dermatoses, including AE.
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