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系统性红斑狼疮患者中 STAT3/IL-17 的表达上调。

Upregulated expression of STAT3/IL-17 in patients with systemic lupus erythematosus.

机构信息

Section of Rheumatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.

Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.

出版信息

Clin Rheumatol. 2019 May;38(5):1361-1366. doi: 10.1007/s10067-019-04467-8. Epub 2019 Feb 15.

Abstract

Elevated IL-17 levels with higher Th17 numbers are identified in systemic lupus erythematosus (SLE). STAT3 signaling plays a crucial role in the Th17 generation, and SOCS3 negatively regulates their formation. We investigated IL-17, STAT3, and SOCS3 expression, and analyzed their correlations to elucidate the regulatory mechanisms of IL-17 production in SLE. This study enrolled 32 patients, and venous mononuclear cells (MNCs) were isolated with further purification of CD4-positive T cells. IL-17 and SOCS3 levels were measured by real-time quantitative PCR, and pSTAT3/STAT3 expression was analyzed by immunoblot. Elevated IL-17 and SOCS3 levels were identified in lupus patients. There were higher IL-17 levels in lupus nephritis (class IV) than in SLE without renal involvement. Positive correlations were found between IL-17 levels and SOCS3 expression, lupus activity (SLEDAI-2K), or daily proteinuria. There were higher intensities of pSTAT3/β-actin and STAT3/β-actin in SLE, and a positive correlation between IL-17 expression and pSTAT3/β-actin or STAT3/β-actin intensity. Lupus nephritis (class IV) had higher STAT3/β-actin intensity than SLE without renal involvement. These results suggest upregulated STAT3/IL-17 expression in lupus patients. Such findings might facilitate the development of novel compounds and the application of existing therapeutics targeting the STAT3/IL-17 signal in SLE.

摘要

系统性红斑狼疮(SLE)患者的白细胞介素 17(IL-17)水平升高,Th17 数量增加。STAT3 信号在 Th17 细胞的产生中起着关键作用,而 SOCS3 则负向调节其形成。我们研究了 IL-17、STAT3 和 SOCS3 的表达,并分析了它们之间的相关性,以阐明 SLE 中 IL-17 产生的调节机制。本研究纳入了 32 名患者,分离静脉单核细胞(MNCs),进一步纯化 CD4+T 细胞。通过实时定量 PCR 测量 IL-17 和 SOCS3 水平,通过免疫印迹分析 pSTAT3/STAT3 表达。狼疮患者的 IL-17 和 SOCS3 水平升高。狼疮肾炎(IV 级)患者的 IL-17 水平高于无肾脏受累的 SLE 患者。IL-17 水平与 SOCS3 表达、狼疮活动度(SLEDAI-2K)或每日蛋白尿呈正相关。SLE 患者的 pSTAT3/β-actin 和 STAT3/β-actin 强度较高,IL-17 表达与 pSTAT3/β-actin 或 STAT3/β-actin 强度呈正相关。狼疮肾炎(IV 级)患者的 STAT3/β-actin 强度高于无肾脏受累的 SLE 患者。这些结果表明狼疮患者的 STAT3/IL-17 表达上调。这些发现可能有助于开发针对 STAT3/IL-17 信号的新型化合物,并应用现有的治疗方法治疗 SLE。

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