DATS通过NF-κB抑制LPS诱导小鼠肺泡巨噬细胞促炎细胞因子表达  

DATS inhibited LPS-induced proinflammatory cytokines expression in mouse alveolar macrophages cell line MH-S by inhibiting NF-κB activation

作　　者：朱桂军[1] 李淑瑾[2] 胡振杰[1] 于占彪[3] 张玉想[1] 张勇[1] 

机构地区：[1]河北医科大学第四医院ICU,河北石家庄050011 [2]河北医科大学法医学系,河北石家庄050017 [3]河北大学附属医院ICU,河北保定071000

出　　处：《中国药理学通报》2007年第12期1580-1584,共5页Chinese Pharmacological Bulletin

基　　金：河北省科技攻关资助项目(No05276101D-65)

摘　　要：目的探讨二烯丙基三硫(DATS)抑制脂多糖(LPS)诱导小鼠肺泡巨噬细胞肿瘤坏死因子-α(TNF-α)及白介素-1β表达的信号转导机制。方法体外培养MH-S细胞,用DATS和(或)LPS进行干预。反转录PCR检测细胞中TNF-α、IL-1β mRNA表达,电泳迁移率改变分析(EMSA)检测细胞核因子-κB(NF-κB)活性,Western blot检测细胞磷酸化(p-IκB)及非磷酸化IκB的表达。结果LPS刺激MH-S细胞可导致TNF-α、IL-1β mRNA、p-IκB表达增加及NF-κB活性升高。用DATS(0.1、0.5、2.5、5.0mg.L-1)预处理细胞30min后再给予LPS刺激,可使TNF-α、IL-1β mRNA表达降低,并呈剂量依赖性;升高的NF-κB活性及p-IκB表达均显不同程度的抑制。单独DATS对TNF-α、IL-1β mRNA表达及NF-κB活性无影响。结论DATS可通过抑制IκB磷酸化及NF-κB活化,进而下调LPS诱导小鼠肺泡巨噬细胞TNF-α、IL-1β mRNA表达。Aim To investigate the signal transduction mechanisms of diallyl trisulfide（DATS） inhibiting the tumor necrosis factor （TNF-α） and interleukin-1β （ IL-1β） expression induced by lipopolysaccharide （ LPS ） in mouse alveolar macrophages cell line MH-S. Methods MH-S cells were cultured in vitro, and treated with DATS in the presence or absence of LPS for different time. The expressions of TNF-α mRNA and IL-1β mRNA were detected with reverse transcription-PCR （RT-PCR）. NF-κB activity in MH-S was detected by electrophoresis mobility shift assay （ EMSA ）. The expression of phospho-IκB （p-IκB） and IκB were assayed by Western blot. Results The expressions of TNF-α mRNA, IL-1β mRNA, NF-κB activity and the p-IκB expression in MH-S increased markedly under the stimulation of LPS. Pretreatment with DATS （0. 1, 0. 5, 2.5,5.0 mg·L^-1 ） for 30 min prior to LPS activation resulted in an obvious reduction of TNF-α mRNA, IL-1β mRNA expressions, NF-κB activity and the p-IκB expressions in a dose-dependent manner. DATS alone did not influence the TNF-α and IL-1β mRNA expressions and NF-κB activity. Conclusions DATS down-regulates TNF-α and IL-1β mRNA expressions in LPS-stimulated MH-S by inhibiting the phosphorylation of IκB and the subsequent NF-κB activation.

关 键 词：二烯丙基三硫 脂多糖 肺泡巨噬细胞 细胞因子 核因子-ΚB 

分 类 号：R-332[医药卫生] R284.1