A pathophysiological role of macrophage migration

巨噬细胞迁移的病理生理学作用

• 批准号: 11470395
• 负责人: SAKAMOTO Wataru
• 金额: $ 2.82万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470395/
• 关键词: Macrophage; Macrophage migration inhibitory factor (MIF); Fibroblast; Periodontal disease; Lipopolysaccharide; TNF-α; IL-6; PGE_2

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.

巨噬细胞移动抑制因子（MIF）是由巨噬细胞、T细胞和脑垂体在炎症反应期间释放的多效细胞因子。为了阐明MIF在牙周病中的病理生理作用，我们研究了牙龈组织中多种炎症介质如PGE_2、IL-6、TNF-α和基质金属蛋白酶与MIF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（低于30 pg/ml）。而注射LPS几乎不增加MIF水平（417.7±209.9 ng/ml; 427.1 ± 53.0 ng/ml）。另一方面，通过对H_2O_2和脂多糖刺激的人成纤维细胞的台盼蓝拒染、甲瓒形成、形态学改变和Westren印迹分析，阐明了MIF的分泌主要是由于细胞死亡和随后的细胞内MIF的渗漏所致。这些结果表明，MIF分泌不同于其他炎症细胞因子，如IL-6和TNF-α。

项目成果

坂本亘: "マクロファージ(医学のあゆみ)"医歯薬出版株式会社. 129(9) (1999)

坂本涉：《巨噬细胞（医学史）》石药出版有限公司 129(9) (1999)

W.Sakamoto et al.: "T-kininogen and a 45 kDa proteinase from porphyromonas gingivalis."Immunopharmacology. 45. 159-162 (1999)

W.Sakamoto 等人：“T-激肽原和来自牙龈卟啉单胞菌的 45 kDa 蛋白酶。”免疫药理学。

J. Nishihira, et al.: "The role of macrophage migration inhibitory factor in plasminogen activator system"Annals of Hematology. 79. A11 (2000)

J. Nishihira 等人：“巨噬细胞迁移抑制因子在纤溶酶原激活剂系统中的作用”《血液学年鉴》。

W.Sakamoto et al.: "Coffee and fitness-Coffee suppresses LPS-induced liver injury in rats"J.Nutr.Sci.Vitaminol.. 46. 316-320 (2000)

W.Sakamoto 等人：“咖啡和健身——咖啡抑制 LPS 诱导的大鼠肝损伤”J.Nutr.Sci.Vitaminol.. 46. 316-320 (2000)

J.Nishihira et al.: "Induction of T-kininogen and TNF-α by macrophage migration inhibitory factor in vivo "Seminars in Thrombosis and Hemostasis. 25. 557-562 (1999)

J. Nishihira 等人：“体内巨噬细胞迁移抑制因子诱导 T-激肽原和 TNF-α”血栓形成和止血研讨会 25. 557-562 (1999)。