MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection.
MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection.
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DOI：
10.1186/s12866-014-0230-6
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发表时间：
2014-09-02
期刊：
影响因子：
4.2
通讯作者：
Meyer R
中科院分区：
文献类型：
--
作者：
de Souza AP;Vale VL;Silva Mda C;Araújo IB;Trindade SC;de Moura-Costa LF;Rodrigues GC;Sales TS;dos Santos HA;de Carvalho-Filho PC;de Oliveira-Neto MG;Schaer RE;Meyer R
干酪性淋巴结炎(CL)是由假结核棒状杆菌引起的一种小型反刍动物传染病。它的特点是在感染动物的淋巴结和肠道内由炎性细胞因子诱导形成脓肿。白介素10、肿瘤坏死因子α、白介素4和干扰素γ等细胞因子的产生受丝裂原活化蛋白激酶途径的调节。本研究探讨了MAPK通路(MAPK p38、ERK 1和ERK 2)在假性结核杆菌感染60天过程中诱导细胞因子产生的作用。将n = 2 5小鼠随机分为3组，分别接种10 2个减毒株T1的集落形成单位、10 2个集落形成单位的强毒株VD5 7的集落形成单位或无菌生理盐水，分别于30或6 0d后处死。用特异性抑制剂(MAPK p38抑制剂、ERK 1/2抑制剂或ERK 2抑制剂)处理小鼠脾细胞，并与病原菌分泌性抗原(SET1或SeVD57)共同培养。在分泌性抗原的刺激下，MAPK通路参与了IL-10的产生，而MAPKp38和ERK1通路主要参与了肿瘤坏死因子α的产生。而MAPKp38和ERK1、2通路不参与干扰素-γ的产生，而ERK2通路仅在感染VD57的小鼠脾细胞中参与IL-4的产生。作者推测，在假结核杆菌感染下，与肿瘤坏死因子α产生有关的MAPKp38和ERK1通路，以及与IL-10产生有关的MAPKp38和ERK1和2通路是细胞应答的重要调节因子。此外，在受这两种分泌/排泄抗原刺激的感染小鼠细胞中，缺少MAPKp38和ERK1/2途径的干扰素-γ的产生，而在强毒株感染60d期间，在SET1抗原的刺激下，IL-4的产生仅通过ERK2途径参与，这表明这些途径调节着CBA小鼠脾细胞中促炎和调节性细胞因子的产生。
Caseous lymphadenitis (CL) is a contagious infectious disease of small ruminants caused by Corynebacterium pseudotuberculosis. Is characterized by the formation of abscesses in the lymph nodes and intestines of infected animals, induced by inflammatory cytokines. The production of cytokines, such as IL-10, TNF-α, IL-4 and IFN-γ, is regulated by mitogen-activated protein kinase (MAPK) pathway activation. The present study investigated the involvement of MAPK pathways (MAPK p38, ERK 1 and ERK 2) with respect to the production of cytokines induced by antigens secreted by C. pseudotuberculosis over a 60-day course of infection. CBA mice (n = 25) were divided into three groups and infected with 102 colony forming units (CFU) of attenuated strain T1, 102 CFU of virulent strain VD57 or sterile saline solution and euthanized after 30 or 60 days. Murine splenocytes were treated with specific inhibitors (MAPK p38 inhibitor, ERK 1/2 inhibitor or ERK 2 inhibitor) and cultured with secreted antigens obtained from pathogenic bacteria (SeT1 or SeVD57). The MAPK pathways evaluated were observed to be involved in the production of IL-10, under stimulation by secreted antigens, while the MAPK p38 and ERK 1 pathways were shown to be primarily involved in TNF-α production. By contrast, no involvement of the MAPK p38 and ERK 1 and 2 pathways was observed in IFN-γ production, while the ERK 2 pathway demonstrated involvement in IL-4 production only in the mouse splenocytes infected with VD57 under stimulation by SeT1. The authors hypothesize that MAPK p38 and ERK 1 pathways with respect to TNF-α production, as well as the MAPK p38 and ERK 1 and 2 pathways in relation to IL-10 production under infection by C. pseudotuberculosis are important regulators of cellular response. Additionally, the lack of the MAPK p38 and ERK 1/2 pathways in IFN-γ production in infected CBA murine cells stimulated with the two secreted/excreted antigens, in IL-4 production showing involvement only via the ERK 2 pathway under stimulation by SeT1 antigen during 60-day infection period with the virulent strain, suggests that these pathways regulated the production of pro-inflammatory and regulatory cytokines in the splenic cells of CBA mice.
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