成年大鼠星形细胞经LPS、前炎症因子和免疫调节因子刺激后β-趋化因子的分泌

Secretion of β chemokine from the adult rat astrocytes stimulated by LPS, proinflammatory cytokines and immunoregulatory cytokines

目的研究在中枢神经系统（ＣＮＳ）的炎症性疾病中，作为构成血脑屏障结构的组成部分之一，可引起白细胞浸润的星形细胞分泌趋化因子的影响因素。方法通过星形细胞体外培养，经不同细胞因子刺激，用原位杂交检测成年大鼠星形细胞β－家系趋化因子的ｍＲＮＡ表达。结果ＩＦＮ－γ可引起ＭＣＰ－１，ＲＡＮＴＥＳ，ＭＩＰ－１α和ＭＩＰ－１β的ｍＲＮＡ表达；ＴＮＦ－α可引起ＲＡＮＴＥＳ和ＭＩＰ－１β的ｍＲＮＡ表达；ＬＰＳ可引起ＭＩＰ－１α和ＭＩＰ－１β的ｍＲＮＡ表达。ＴＧＦ－β和ＩＬ－１０下调由ＬＰＳ引起的ＭＣＰ－１和ＭＩＰ－１α和ＭＩＰ－１βｍＲＮＡ表达。ＴＧＦ－β和ＩＬ－１０可抑制由ＴＮＦ－α引起的ＭＣＰ－１和ＲＡＮＴＥＳ的ｍＲＮＡ表达。ＩＬ－１０还可下调由ＴＮＦ－α引起的ＭＩＰ－１βｍＲＮＡ表达。结论成年大鼠体外试验中的星形细胞可由ＬＰＳ和前炎症因子刺激，产生β－家系趋化因子ｍＲＮＡ的表达。而调节因子如ＴＧＦ－β和ＩＬ－１０可抑制由ＩＦＮ－γ、ＴＮＦ－α和ＬＰＳ引起的β－家系趋化因子的ｍＲＮＡ表达。

Objective To investigate factor(s) regulating astrocyte chemokine expression, we examined the induction of β chemokine mRNA expression in adult rat astrocytes. Methods By in situ hybridization, we determined the β family chemokine mRNA expression in the astrocytes which were cultivated in vitro and stimulated with different agents. Results Astrocyte derived MCP 1, RANTES, MIP 1α and MIP 1β mRNA were easily induced by IFN γ. TNF α induced RANTES and MIP 1β mRNA expression, and LPS induced MIP 1α and MIP 1β mRNA expression in astrocytes. LPS induced MCP 1 and RANTES mRNA expression by astrocytes were antagonized by TGF β and IL 10. TGF β and IL 10 also down regulated MCP 1 mRNA expression induced by TNF α, and IL 10, but not TGF β, inhibited MIP 1β mRNA expression induced by TNF α. Conclusions The results of this in vitro study suggest that β chemokine mRNA expression by adult rat astrocytes can be induced by LPS or proinflammatory cytokines, while regulatory cytokines, such as TGF β and IL 10, down regulate the induction of astrocyte derived β family chemokine mRNA expression induced by LPS, IFN γ and TNF α.