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H2S 瞬时抑制类风湿关节炎成纤维样滑膜细胞中 IL-6 的表达并使 p44/42 丝裂原活化蛋白激酶失活。

H2S transiently blocks IL-6 expression in rheumatoid arthritic fibroblast-like synoviocytes and deactivates p44/42 mitogen-activated protein kinase.

机构信息

Ludwig Boltzmann Institute for Rheumatology and Balneology, Vienna, Austria.

出版信息

Cell Biol Int. 2010 Mar 29;34(5):477-84. doi: 10.1042/CBI20090436.

DOI:10.1042/CBI20090436
PMID:20067446
Abstract

Sulfur bath therapy represents the oldest form of treatment for patients with different types of rheumatic disorders. However, scientific reports about the beneficial effects of this form of therapy are controversial, rare and of poor scientific quality. Also, little is known about the role and underlying molecular mechanisms of H2S. Therefore, this topic encouraged us to investigate the influence of H2S on fibroblasts isolated from the synovial membrane of RA (rheumatoid arthritis) patients. FLSs (fibroblast-like synoviocytes) were treated with different concentrations of an exogenous H2S donor (NaHS). At defined time points, secretion of IL-6 was quantified by ELISA. Activation/deactivation of MAPKs (mitogen-activated protein kinases), p38 and p44/42 MAPK (ERK1/2) were confirmed by Western blot experiments. FLSs constitutively express and secrete large quantities of IL-6 and IL-8. Data provided prove that, in FLSs, constitutive as well as IL-1beta-induced expression of IL-6 is transiently and partially down-regulated by the short treatment of cells with low concentrations of NaHS. Another key finding is that H2S deactivates p44/42 MAPK (ERK1/2). Long-term exposure of FLSs to H2S provides stimulatory effects, leading to reinforced activation of p38 MAPK and ERK1/2 accompanied by upregulation of IL-6 expression. Presented data seem of importance for studying (patho-) physiological functions of H2S and also for re-evaluating sulfur spa therapy as one of the oldest forms of therapy for rheumatic disorders.

摘要

硫磺浴疗法代表了治疗不同类型风湿性疾病患者的最古老形式。然而,关于这种治疗形式的有益效果的科学报告是有争议的、罕见的,且科学质量较差。此外,关于 H2S 的作用和潜在分子机制知之甚少。因此,这个主题促使我们研究 H2S 对来自类风湿关节炎(RA)患者滑膜的成纤维细胞的影响。成纤维细胞样滑膜细胞(FLSs)用不同浓度的外源性 H2S 供体(NaHS)处理。在定义的时间点,通过 ELISA 定量测定 IL-6 的分泌。通过 Western blot 实验证实 MAPKs(有丝分裂原激活的蛋白激酶)、p38 和 p44/42 MAPK(ERK1/2)的激活/失活。FLSs 持续表达和分泌大量的 IL-6 和 IL-8。提供的数据证明,在 FLSs 中,IL-1β诱导的 IL-6 的组成型表达以及短暂地部分被低浓度 NaHS 处理细胞所下调。另一个关键发现是 H2S 失活了 p44/42 MAPK(ERK1/2)。FLSs 长期暴露于 H2S 会产生刺激作用,导致 p38 MAPK 和 ERK1/2 的激活增强,同时伴随着 IL-6 表达的上调。目前的数据似乎对研究 H2S 的(病理)生理功能以及重新评估硫磺浴疗法作为治疗风湿性疾病的最古老形式之一具有重要意义。

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