The metastasis promoting protein S100A4 is increased in idiopathic inflammatory myopathies
The metastasis promoting protein S100A4 is increased in idiopathic inflammatory myopathies
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DOI：
10.1093/rheumatology/ker218
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发表时间：
2011-10-01
期刊：
影响因子：
5.5
通讯作者：
Senolt, Ladislav
中科院分区：
文献类型：
--
作者：
Cerezo, Lucie Andres;Kuncova, Klara;Senolt, Ladislav
目标. S100 A4蛋白被认为是一种转移促进因子;然而，最近已经描述了其参与非恶性疾病如RA和银屑病。本研究旨在探讨S100 A4在特发性炎性肌病中的表达及其可能的作用。采用免疫组化方法检测11例正常人、8例PM和6例DM患者的肌肉组织中S100 A4蛋白的表达。IF染色用于将S100 A4与选择的细胞共定位。RT-PCR和ELISA检测S100 A4处理后细胞因子表达和蛋白质合成。与对照个体相比，S100 A4蛋白在炎性肌病患者肌肉组织中显著上调，并且特别与单核细胞浸润的存在相关。在PM/DM中仅有少量再生肌纤维表达S100 A4。然后我们分析了S100 A4对人心肌细胞和外周血单个核细胞（PBMCs）的作用。虽然S100 A4不影响肌细胞，但用S100 A4刺激PBMC显著诱导TNF-α、IL-1 β和IL-6的表达和合成，但不诱导IFN-α的表达和合成。我们发现S100 A4不直接参与穿孔素/颗粒酶B诱导的细胞凋亡，也不调节心肌细胞和PBMC中Bax和Bcl 2 mRNA的表达。S100 A4在发炎肌肉组织中的表达增加突出了其在炎性肌病发病机制中的潜在作用。S100 A4可能作为一种类胡萝卜素因子，通过刺激单核细胞增加促炎细胞因子的合成，间接促进肌纤维损伤。
Objectives. The S100A4 protein is known as a metastasis promoting factor; however, its involvement in non-malignant diseases such as RA and psoriasis has been recently described. The aim of this study was to investigate the expression and possible role of S100A4 in idiopathic inflammatory myopathies.Methods. S100A4 protein expression was detected by immunohistochemistry in muscle tissue from control individuals (n = 11) and patients with PM and DM (n = 8/6). IF staining was used to co-localize S100A4 with selected cells. Cytokine expression and protein synthesis in S100A4-treated cells were analysed by RT-PCR and ELISA.Results. S100A4 protein was significantly up-regulated in muscle tissue of patients with inflammatory myopathies compared with control individuals and was associated particularly with the presence of mononuclear infiltrates. Only few regenerating muscle fibres in PM/DM expressed S100A4. Then we analysed the effect of S100A4 on human myocytes and peripheral blood mononuclear cells (PBMCs). Although S100A4 did not affect myocytes, stimulation of PBMCs with S100A4 significantly induced the expression and synthesis of TNF-alpha, IL-1 beta and IL-6, but not of IFN-alpha. We showed that S100A4 is not directly involved in perforin/granzyme B-induced apoptosis and that it does not modulate the expression of Bax and Bcl2 mRNA in myocytes and PBMCs.Conclusion. Increased expression of S100A4 in inflamed muscle tissue highlights its potential role in the pathogenesis of inflammatory myopathies. S100A4 may act as a cytokine-like factor indirectly promoting muscle fibre damage by stimulating mononuclear cells to increase the synthesis of pro-inflammatory cytokines.