A pathophysiological role of macrophage migration

巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）是巨噬细胞、t细胞和脑垂体在炎症反应中释放的一种多用途细胞因子。为了阐明MIF在牙周病中的病理生理作用，我们研究了MIF与牙龈组织中多种炎症介质PGE_2、IL-6、TNF-α和基质金属蛋白酶的关系。MIF在正常和炎症牙龈组织中均有表达。有趣的是，lps注射导致血清IL-6（12.6±4.2 ng/ml）和TNF-α（4.6±3.8 ng/ml）水平升高，尽管这些细胞因子在正常大鼠血清中未检测到（小于30 pg/ml）。而注射LPS后MIF水平几乎没有升高（未注射组为417.7±209.9 ng/ml；注射LPS组为427.1±53.0 ng/ml）。另一方面，通过对H_2O_2和脂多糖刺激的人培养成纤维细胞的台班蓝排斥、甲酸形成、形态学变化和western blot分析，阐明了MIF的分泌主要是由于细胞死亡和细胞内MIF的渗漏。这些结果表明，MIF的分泌不同于其他炎症细胞因子，如IL-6和TNF-α。

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine released by macrophages, T-cells, and the pituitary gland during inflammatory responses. In order to clarify the pathophysiological roles of MIF in periodontal disease, we investigated relationship between MIF and a variety of inflammatory mediators, such as PGE_2, IL-6, TNF-α, and matrix metalloproteinase in gingival tissues. MIF was expressed in both normal and inflamed gingival tissues. Interestingly, LPS-injection led to increased serum levels of IL-6 (12.6 ± 4.2 ng/ml) and TNF-α (4.6 ± 3.8 ng/ml), although these cytokines were not detceted in normal rat serum (less than 30 pg/ml). However, MIF level was hardly increased by LPS injection (417.7±209.9 ng/ml in non-injection ; 427.1 ± 53.0 ng/ml in LPS-injection). On the other hand, it was clarified that MIF secretion seems to be due to mainly cell-death and subsequently leakage of intracellular MIF, by analyses of trypan blue exclusion, formazan formation, morphological changes, and Westren blot in human cultured fibroblasts stimulated with H_2O_2 and lipopolysaccharides. These results indicate that MIF secretion differs from other inflammatory cytokines such as IL-6 and TNF-α.