MIF调节巨噬细胞系RAW264.7中TNF-alpha Ⅱ型受体的表达

MIF Regulates TNF Alpha Receptor Type Ⅱ Expression in RAW264.7 Cells

巨噬细胞迁移抑制因子(MIF)在调节固有免疫和获得性免疫中发挥重要作用,在炎症、败血症和自身免疫疾病中都有它的参与.MIF可以刺激巨噬细胞表达TNF-α、IL-1#、IL-6和IL-8等多种细胞因子.在最近的研究中发现,外源性的MIF可以上调RAW264.7细胞中TNF-αⅡ型受体的mRNA水平,细胞自分泌的MIF对维持TNF-αⅡ型受体的基线水平有很大作用.这种调节作用可以被Src和JNK抑制剂所阻断.在巨噬细胞活化过程中,MIF这一新发现的功能提示它在放大炎症信号的同时,还能消减TNF-α可能引起的凋亡和细胞毒等副作用.

Macrophage migration inhibitory factor （MIF） plays an important role in the regulation of the innate and adaptive immunity and is implicated in inflammation, sepsis and autoimmune disease. Previous works have shown that MIF could induce the expression of many cytokines, such as TNF-α, IL-1β, IL-6 and IL-8 in macrophage. It was reported here that MIF up-regulates the type IT TNF-α receptor （p75 TNFR） expression at mRNA level in RAW264.7 cell line. When RAW264.7 cells were treated with MIF inhibitor, antibody neutralizing MIF activities or the siRNA specific to MIF receptor CD74, the baseline TNFR Ⅱ mRNA level was reduced. Using inhibitors specific to Erk, JNK, p38, Src or PKA, it was demonstrated that MIF regulation of TNFR Ⅱ mRNA expression is mediated by Src and JNK. The up-regulation of the TNF-α type Ⅱ receptor by MIF suggests a mechanism of amplifying inflammatory signals while avoiding side effects of TNF-α, such as apoptosis or cytotoxicity during macrophage activation.