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Modulation of Cytokine Profiles by the Mycoplasma SuperantigenMycoplasma arthritidis Mitogen Parallels Susceptibility to Arthritis Induced by M. arthritidis

机译:支原体超抗原对细胞因子谱的调节支原体支原体有丝分裂原平行于由支原体支原体引起的关节炎敏感性

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Mycoplasma arthritidis mitogen (MAM) is a potent superantigen secreted by M. arthritidis, an agent of murine arthritis. Here we compare the abilities of MAM to induce a panel of cytokines in vitro and in vivo in BALB/c and C3H/HeJ mouse strains that differ in susceptibility to mycoplasmal arthritis. Splenocytes from both mouse strains produced high levels of all cytokines by 24 h following in vitro exposure to MAM. No differences in cytokine profiles were seen irrespective of the MAM dose. However, there were striking differences in cytokine profiles present in supernatants of splenocytes that had been collected from mice after intravenous (i.v.) injection of MAM and subsequently rechallenged with MAM in vitro. Splenocytes collected 24 and 72 h after i.v. injection of MAM and challenged in vitro with MAM showed the most marked divergence in the secreted cytokines. Type 1 cytokines were markedly elevated in C3H/HeJ cell supernatants, whereas they were depressed or remained low in BALB/c cell supernatants. In contrast, the levels of type 2 cytokines were all greatly increased in BALB/c cell cultures but were decreased or remained low in C3H/HeJ supernatants. Interleukin-12 mRNA and protein was also markedly elevated in C3H/HeJ mice, as were the levels of immunoglobulin G2a. The data indicate a major skewing in cytokine profiles to a type 1 inflammatory response in C3H/HeJ mice but to a protective type 2 response in BALB/c mice. These cytokine changes appear to be associated with the severe arthritis in C3H/HeJ mice following injection of M. arthritidis in comparison to the mild disease seen in injected BALB/c mice.
机译:支原体关节炎有丝分裂原(MAM)是一种由鼠关节炎支原体分泌的强效超抗原。在这里,我们比较了MAM在对支原体关节炎敏感性不同的BALB / c和C3H / HeJ小鼠品系中在体外和体内诱导一系列细胞因子的能力。在体外暴露于MAM后24小时,两种小鼠品系的脾细胞均产生了高水平的所有细胞因子。不论MAM剂量如何,均未观察到细胞因子谱的差异。然而,在静脉内(i.v.)注射MAM并随后在体外用MAM激发后,从小鼠收集的脾细胞上清液中存在的细胞因子谱存在显着差异。静脉注射后24和72小时收集脾细胞。注射MAM并在体外用MAM攻击后,分泌的细胞因子差异最大。 C3H / HeJ细胞上清液中1型细胞因子显着升高,而BALB / c细胞上清液中1型细胞因子低下或保持较低水平。相比之下,BALB / c细胞培养物中2型细胞因子的水平都大大增加,但在C3H / HeJ上清液中则降低或保持较低水平。在C3H / HeJ小鼠中,白细胞介素12 mRNA和蛋白也显着升高,免疫球蛋白G2a的水平也升高。数据表明,细胞因子概况在C3H / HeJ小鼠中主要针对1型炎症反应而在BALB / c小鼠中针对保护性2型反应。与注射BALB / c小鼠中发现的轻度疾病相比,注射M. arthritidis后,这些细胞因子的变化似乎与C3H / HeJ小鼠中的严重关节炎有关。

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