Ishiguro Yoh, Ohkawara Tatsuya, Sakuraba Hirotake, Yamagata Kazufumi, Hiraga Hiroto, Yamaguchi Satoko, Fukuda Shinsaku, Munakata Akihiro, Nakane Akio, Nishihira Jun
First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Clin Immunol. 2006 Sep;120(3):335-41. doi: 10.1016/j.clim.2006.05.010. Epub 2006 Jun 27.
Macrophage migration inhibitory factor (MIF) is a cytokine that has potent anti-steroid effects and might be implicated in the pathogenesis of Ulecrative colitis (UC). We defined the functional role of MIF in the glucocorticoid (GC)-resistant inflammatory response in UC. Twenty-four colonic samples were obtained from GC responsive cases, GC refractory cases, Crohn's disease and controls. LPMC were isolated from surgical specimens. MIF was strongly expressed at mRNA levels in refractory cases rather than responsive cases with UC and controls. IL-8 production from LPMC was significantly reduced by GC addition in responsive cases but not in refractory cases. In refractory cases, anti-MIF Ab ameliorated GC-resistant IL-8 production and p38-MAPK activity of LPMC. In addition, p38-MAPK antagonist SB230580 also ameliorated GC-resistant IL-8 production. These results suggest that MIF has an additional proinflammatory activity through the p38-MAPK pathway in GC-resistant UC.
巨噬细胞移动抑制因子（MIF）是一种具有强大抗类固醇作用的细胞因子，可能与溃疡性结肠炎（UC）的发病机制有关。我们确定了MIF在UC糖皮质激素（GC）抵抗性炎症反应中的功能作用。从GC反应性病例、GC难治性病例、克罗恩病患者及对照者中获取了24份结肠样本。从手术标本中分离出淋巴细胞性脉络丛脑膜炎病毒（LPMC）。MIF在难治性病例的mRNA水平上强烈表达，而非UC反应性病例和对照者。在反应性病例中，添加GC可显著降低LPMC产生的白细胞介素-8，但在难治性病例中则不然。在难治性病例中，抗MIF抗体可改善LPMC的GC抵抗性白细胞介素-8产生及p38丝裂原活化蛋白激酶（p38-MAPK）活性。此外，p38-MAPK拮抗剂SB230580也可改善GC抵抗性白细胞介素-8的产生。这些结果表明，在GC抵抗性UC中，MIF通过p38-MAPK途径具有额外的促炎活性。
