Petro Thomas M
Department of Oral Biology, the Nebraska Center for Virology, University of Nebraska Medical Center, Lincoln, NE 68583, USA.
Immunol Lett. 2005 Feb 15;97(1):47-53. doi: 10.1016/j.imlet.2004.09.013.
Theiler's murine encephalomyelitis virus (TMEV) infection of macrophages induces a demyelinating disease (DD) in certain strains of mice that is similar to human multiple sclerosis. In contrast to IFN-beta, expression of IL-23 p19 and p40 subunits by macrophages in response to TMEV may contribute to DD. TMEV infection of macrophages likely induces IL-23 and IFN-beta by activating p38 or ERK MAP-kinases (MAPK) and the p38 substrate ATF-2 within 30 min. To determine the role of MAPKs in TMEV-induced IL-23 and IFN-beta expression, RAW264.7 cells were pretreated with SB203580 or U0126, inhibitors of p38 and ERK MAPKs, respectively. SB203580 significantly increased TMEV-induced p19 but decreased p40 expression. In contrast, U0126 decreased p19 and increased TMEV-induced p40 and IFN-beta expression. Interestingly, U0126 prolonged TMEV-induced ATF-2 activation to at least 3h. Thus ERK MAPKs regulate expression of TMEV-induced p19 differently than p40 and IFN-beta suggesting the benefits of U0126 in treatment of DD.
巨噬细胞感染泰勒氏鼠脑脊髓炎病毒（TMEV）会在某些品系的小鼠中诱发一种脱髓鞘疾病（DD），该疾病与人类多发性硬化症相似。与干扰素-β 不同，巨噬细胞在响应 TMEV 时表达的白细胞介素-23 p19 和 p40 亚基可能与 DD 有关。巨噬细胞感染 TMEV 可能会在 30 分钟内通过激活 p38 或细胞外调节蛋白激酶（ERK）丝裂原活化蛋白激酶（MAPK）以及 p38 底物活化转录因子-2（ATF-2）来诱导白细胞介素-23 和干扰素-β。为了确定 MAPK 在 TMEV 诱导的白细胞介素-23 和干扰素-β 表达中的作用，分别用 p38 和 ERK MAPK 的抑制剂 SB203580 或 U0126 预处理 RAW264.7 细胞。SB203580 显著增加了 TMEV 诱导的 p19 表达，但降低了 p40 表达。相比之下，U0126 降低了 p19 表达，并增加了 TMEV 诱导的 p40 和干扰素-β 表达。有趣的是，U0126 将 TMEV 诱导的 ATF-2 激活延长至至少 3 小时。因此，ERK MAPK 对 TMEV 诱导的 p19 表达的调节方式与 p40 和干扰素-β 不同，这表明 U0126 在治疗 DD 方面具有益处。
