DATS通过p38MAPK通路抑制LPS诱导的小鼠MH-S细胞TNF-α及IL-1β表达  

Inhibition of LPS-induced TNF-α and IL-1β expression by DATS through p38 MAPK pathway in MH-S cell

作　　者：朱桂军[1] 孟志强[2] 刘丽霞[1] 武新慧[1] 王澜涛[1] 陈玉红[1] 胡振杰[1] 

机构地区：[1]河北医科大学第四医院重症医学科,河北石家庄050011 [2]邢台医学高等专科学校,河北邢台054000

出　　处：《中国药理学通报》2012年第9期1303-1307,共5页Chinese Pharmacological Bulletin

基　　金：河北省科技攻关资助项目(No 05276101D-65)

摘　　要：目的探讨p38MAPK在二烯丙基三硫(DATS)抑制脂多糖(LPS)诱导小鼠肺泡巨噬细胞促炎细胞因子表达中的作用。方法体外培养MH-S细胞,用DATS和(或)LPS进行干预,Western blot检测细胞p38及磷酸化p38(p-p38)的表达;用LPS和(或)SB203580孵育细胞,反转录PCR检测细胞中TNF-α、IL-1βmRNA表达,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p-p38表达增加,呈时间依赖性;用DATS(0.1、0.5、2.5、5.0 mg.L-1)预处理细胞30 min后再给予LPS刺激,p-p38表达呈剂量依赖性下降;单独DATS对p-p38表达无明显影响。p38特异性抑制剂SB203580可剂量依赖性地抑制LPS诱导的p-IκB蛋白、TNF-α及IL-1βmR-NA表达。结论 DATS可通过抑制p38MAPK通路抑制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-1βmRNA表达。Aim To investigate the role of p38 mitogen activated protein kinase （MAPK） in the signal transduction mechanisms of diallyl trisulfide （DATS） inhibiting the tumor necrosis factor （TNF-α） and interleukin-1 β （ IL-1β ） expression induced by lipopo-lysaccharide （LPS） in mouse alveolar macrophages cell line MH-S. Methods MH-S ceils were cultured in vitro, and treated with DATS in the presence or absence of LPS for different time. The expression of phospho- p 3 8 and p38 were assayed by Western blot.MH-S cells were incubated with specific p38 inhibitor SB203580 in the presence or absence of LPS. The expression of TNF-α mRNA and IL-1β mRNA were detected with reverse transcription-PCR （RT-PCR）. The expression of phospho-IKB and IKB were assayed by Western blot. Results The expression of the phospho- p38 expression in MH-S increased markedly under the stimulation of LPS in a time-dependent manner. Pretreatment with DATS（0. 1, 0. 5, 2. 5, 5.0 mg · L^-1 ） for 30min prior to LPS activation resulted in an obvious reduction of phospho-p38 expression in a dose-dependent manner. DATS alone did not influence the phos-pho-p38 expression. SB203580 dose-dependendy inhibited LPS-induced TNF-α mRNA, IL-1β mRNA expression and phospho-IKB expression. Conclusions DATS downregulates TNF-α and IL-1β mRNA expression in LPS-stimulated MH-S by inhibiting the p38MAPK pathway and the subsequent phosphorylation of κB and NF-κB activation.

关 键 词：二烯丙基三硫 脂多糖 肺泡巨噬细胞 P38丝裂原活化蛋白激酶 核因子-κB 肿瘤坏死因子α 白细胞介素1Β 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]