Roles of IL-1 and TNF-alpha in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells.
Roles of IL-1 and TNF-alpha in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells.
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IL-1 和 TNF-α 在培养的大鼠脑细胞中内毒素诱导的一氧化氮合酶激活中的作用。
DOI：
10.1152/ajpregu.1996.270.2.r326
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Reichlin,S
中科院分区：
文献类型：
--
作者：
Romero,LI;Tatro,JB;Field,JA;Reichlin,S
在星形胶质细胞和小胶质细胞中，细菌脂多糖(LPS)刺激白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和一氧化氮(NO)的产生和释放。尽管IL-1β和肿瘤坏死因子-α本身能够诱导胶质细胞中的一氧化氮合酶(NOS)，但介导内毒素诱导脑内一氧化氮合酶(NOS)的特异性因素尚不清楚。为确定内毒素诱导脑细胞一氧化氮合酶活性是由IL-1还是由肿瘤坏死因子-α介导，单独或联合应用IL-1受体拮抗剂(IL-1ra)和肿瘤坏死因子可溶性受体(TNFsRp55)对内毒素诱导的一氧化氮合酶(NOS)活性的影响。在富含胶质细胞的乳鼠端脑细胞混合原代培养中，内毒素(0.1-100 ng/ml)、IL-1β(0.01-10 nM)和肿瘤坏死因子-α(0.1-100 nM)各浓度均可依赖地刺激亚硝酸盐的积累，亚硝酸盐是NO产生的指标。N omega-硝基-L-精氨酸甲酯和N omega-单甲基-L-精氨酸均能阻断内毒素和IL-1诱导的亚硝酸盐蓄积，提示亚硝酸盐蓄积是由一氧化氮合酶介导的。与IL-1相比，单用肿瘤坏死因子-α诱导的NO生成较弱，但亚高峰浓度的IL-1β(1 NM)和肿瘤坏死因子-α(10 NM)联合应用可协同诱导一氧化氮合酶的产生。此外，TNFsRp55和IL-1ra均可剂量依赖性地部分抑制内毒素诱导的NO反应，且TNFsRp55的作用与IL-1ra相当或大于IL-1ra。TNFsRp55和IL-1ra联合应用的疗效并不明显优于单独使用肿瘤坏死因子-sRp55。结果表明，内毒素诱导脑细胞一氧化氮合酶活性部分是由IL-1β和TNF-α共同介导的。
In astrocytes and microglia, bacterial lipopolysaccharide (LPS) stimulates production and release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO). Although IL-1 beta and TNF-alpha are themselves capable of inducing NO synthase (NOS) in glia, the specific factors mediating LPS induction of NOS in brain have not been identified. To determine whether LPS induction of NOS in brain cells is mediated by IL-1 or TNF-alpha, acting alone or in concert, the effects of IL-1-receptor antagonist (IL-1Ra) and of TNF-soluble receptor (TNFsRp55), presented individually and in combination, on LPS-induced NOS activity were tested. In glial-enriched mixed primary cultures of neonatal rat telencephalic cells, LPS (0.1-100 ng/ml), IL-1 beta (0.01-10 nM), and TNF-alpha (0.1-100 nM) each concentration dependently stimulated accumulation of nitrite, an indicator of NO production. Induction of nitrite accumulation by LPS and by IL-1 was blocked by N omega-nitro-L-arginine methyl ester and N omega-monomethyl-L-arginine, indicating that it was mediated by NOS. TNF-alpha alone induced NO production weakly as compared with IL-1, but combined submaximal concentrations of IL-1 beta (1 nM) and TNF-alpha (10 nM) induced NOS synergistically. Furthermore, TNFsRp55 and IL-1Ra each produced a dose-dependent partial inhibition of the NO response to LPS, and the effect of TNFsRp55 was equal to or greater than that of IL-1Ra. TNFsRp55 and IL-1Ra in combination were not significantly more effective than TNF-sRp55 alone. The results indicate that LPS induction of NOS activity in brain cells is mediated in part by both IL-1 beta and TNF-alpha.