糖皮质激素与炎症因子对应急时相反应蛋白SIP24/24p3的协同调控作用及其意义

小鼠应急时相反应蛋白SIP24／24p3有抗炎症和特异性诱导白细胞凋亡的功能,其在体内的表达是高度特异性的。为研究SIP24／24p3的调控因子及机制,我们在小鼠Balb／c3T3和BNL细胞培养中通过灵敏的弱S代谢标记方法检测SIP24／24p3蛋白的表达水平,定量观测分析了糖皮质激素化合物dexamethasone对SIP24／24p3的诱导作用及其与炎症因子白介素6(IL-6)和肿瘤坏死因子α(TNF-α)的协同调控作用。结果显示：(1)在Balb／c3T3和BNL细胞中,dexamethasone对SIP24／24p3都有明显诱导作用,这种诱导作用在BNL细胞中尤其显著;(2)在Balb／c3T3和BNL细胞中dexamethasone与IL-6协同诱导SIP24／24p3;(3)在Balb／c 3T3细胞中dexamethasone与TNF-α对SIP24／24p3有协同诱导效应,而在BNL细胞中dexamethasone与TNF-α对SIP24／24p3的诱导表现为相加效应;(4)在Balb／c3T3和BNL细胞中dexamethasone与IL-6／TNF-α对SIP24／24p3的诱导分别表现出协同和相加效应。多种因子对SIP24／24p3的协同诱导调控有助于阐明其在体内的高度特异表达及机制,SIP24／24p3在不同细胞中的不同表达格局也对体内应急时相反应蛋白在肝脏外和肝脏内的表达方式及诱导机制有提示作用。SIP24／24p3能同时被炎症因子和抗炎症因子诱导的事实显示了其在炎症全过程中的重要作用。

Synergistic regulation of the acute phase protein SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines

SIP24/24p3 is a secreted murine acute phase protein which has been speculated to play an anti-inflammatory role in vivo. Recently SIP24/24p3 has been found to be able to specifically induce apoptosis in leukocytes. By using (35)S metabolic labeling method, we studied the regulation of SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines IL-6 and TNF-alpha in cultured Balb/c 3T3 and BNL cells. The following results were observed: (1) dexamethasone induced the expression of SIP24/24p3 in both Balb/c 3T3 and BNL cells, the induction was more significant in BNL cells; (2) dexamethasone and IL-6 synergistically induced the expression of SIP24/24p3 in both Balb/c 3T3 and BNL cells; (3) in Balb/c 3T3 cells dexamethasone and TNF-alpha acted synergistically to induce the expression of SIP24/24p3, whereas in BNL cells dexamethasone and TNF-alpha induced the expression of SIP24/24p3 in an additive manner; (4) dexamethasone and IL-6/TNF-alpha acted synergistically in Balb/c 3T3 cells and additively in BNL cells to induce the expression of SIP24/24p3. The inducibility of SIP24/24p3 by multiple factors will help to explain its highly specific expression in vivo. The difference in the expression patterns of SIP24/24p3 in different cell types is also suggestive to its expression and regulation in hepatic and extrahepatic tissues. Finally, the fact that SIP24/24p3 protein can be induced by both pro-inflammatory as well as anti-inflammatory factors is indicative of the important role of SIP24/24p3 in the entire acute phase response process.