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勘误:结核分枝杆菌的甘露糖封端脂阿拉伯甘露聚糖通过上调人II型肺泡上皮细胞中的ERK1/2和p38诱导IL-37产生。

Erratum: Mannose-capped lipoarabinomannan from Mycobacterium tuberculosis induces IL-37 production via upregulating ERK1/2 and p38 in human type II alveolar epithelial cells.

作者信息

Huang Zhen, Zhao Gao Wei, Gao Chun Hai, Chi Xiu Wen, Zeng Tao, Hu Yan Wei, Zheng Lei, Wang Qian

机构信息

Laboratory Medicine Center, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong, P. R. China; Department of Laboratory Medicine, Longgang Central District HospitalShenzhen 518116, Guangdong, P. R. China.

Linyi Blood Center Linyi 276000, Shandong, P. R. China.

出版信息

Int J Clin Exp Med. 2015 Oct 15;8(10):19791. eCollection 2015.

Abstract

The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose-capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb. Interleukin (IL)-37, is a newly identified anti-inflammatory cytokine, which reduces systemic and local inflammation. However, the correlation between ManLAM and IL-37 remains unknown. Therefore, in this study, we investigate the possible role and relative molecular mechanism of ManLAM in IL-37 production of human type II alveolar epithelial cells by using A549 cell line. Here, we report that M. tb induced IL-37 mRNA and protein expression in a time-dependent manner. We next fractionated components of M. tb using chloroform: methanol (C:M) and water. In sharp contrast to the C:M phase, water phase was mainly responsible for the production of IL-37. Since ManLAM is the major component of water phase, we found that ManLAM induced IL-37 mRNA and protein expression in a time and dose-dependent manner, while this activity was almost totally abolished by the ERK1/2 (U0126) and p38 (SB203580) inhibitor. ManLAM stimulation significantly induced ERK1/2 and p38 phosphorylation in A549 cells, as well as cell surface TLR2 expression. After interfering TLR2 expression, ERK1/2 and p38 phosphorylation levels were markedly decreased, and also IL-37 production. Though ManLAM also promoted TLR4 expression on A549 cells, TLR4 interference showed no influence on ManLAM-induced IL-37 production. Our results indicate that ManLAM induces IL-37 production in human type II alveolar epithelial cells via up-regulating TLR2/p38 or ERK1/2 pathway, and this provide an important evidence to explain the pathological role of ManLAM that contribute to the persistence of M. tb.[This corrects the article on p. 7279 in vol. 8, PMID: 26221267.].

摘要

结核分枝杆菌(M. tb)的主要表面脂多糖,甘露糖封端的脂阿拉伯甘露聚糖(ManLAM),是M. tb的一种免疫抑制表位。白细胞介素(IL)-37是一种新发现的抗炎细胞因子,可减轻全身和局部炎症。然而,ManLAM与IL-37之间的相关性仍不清楚。因此,在本研究中,我们利用A549细胞系研究了ManLAM在人II型肺泡上皮细胞IL-37产生中的可能作用及相关分子机制。在此,我们报告M. tb以时间依赖性方式诱导IL-37 mRNA和蛋白表达。接下来,我们用氯仿:甲醇(C:M)和水对M. tb的成分进行分级分离。与C:M相形成鲜明对比的是,水相主要负责IL-37的产生。由于ManLAM是水相的主要成分,我们发现ManLAM以时间和剂量依赖性方式诱导IL-37 mRNA和蛋白表达,而这种活性几乎完全被ERK1/2(U0126)和p38(SB203580)抑制剂消除。ManLAM刺激显著诱导A549细胞中ERK1/2和p38磷酸化,以及细胞表面TLR2表达。干扰TLR2表达后,ERK1/2和p38磷酸化水平明显降低,IL-37产生也减少。虽然ManLAM也促进A549细胞上TLR4表达,但TLR4干扰对ManLAM诱导的IL-37产生没有影响。我们的结果表明,ManLAM通过上调TLR2/p38或ERK1/2途径诱导人II型肺泡上皮细胞产生IL-37,这为解释ManLAM在结核分枝杆菌持续存在中的病理作用提供了重要证据。[这纠正了第8卷第7279页的文章,PMID:26221267。]

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