Hui Bin, Geng Mei-yu, Li Jing
Marine Drug and Food Institute, Ocean University of China, Qingdao, China.
Yao Xue Xue Bao. 2006 Apr;41(4):338-41.
To investigate the effects of sulfated polymannuroguluronate (SPMG), a novel candidate anti-AIDS drug in Phase II clinical trial, on Tat-induced release of proinflammatory cytokines (i.e., TNFalpha, IL-1beta and IL-6) and its related mechanism.
The effects of SPMG on Tat induced TNFalpha (4 h), IL-1beta and IL-6 (6 h) secretion in THP-1 cells were measured by ELISA. Western blotting analysis was used to study the effects of SPMG on Tat induced PKCzeta, PKCtheta and PKCsigma phosphorylation.
SPMG (50 to 100 microg x mL(-1)) markedly suppressed TNFalpha, IL-1beta and IL-6 secretion in Tat activated THP-1 cells. In THP-1 cells the phosphorylation levels of PKCzeta, PKCtheta and PKCsigma significantly increased following Tat stimulation, and only PKCsigma phosphorylation levels was inhibited by SPMG (50 to 100 microg x mL(-1)).
SPMG suppresses the secretion of proinflammatory cytokines in THP-1 cells may be by inhibiting PKCsigma activation.
研究处于II期临床试验的新型抗艾滋病药物硫酸化聚甘露糖醛酸（SPMG）对Tat诱导的促炎细胞因子（即肿瘤坏死因子α、白细胞介素-1β和白细胞介素-6）释放的影响及其相关机制。
采用酶联免疫吸附测定法检测SPMG对Tat诱导的THP-1细胞中肿瘤坏死因子α（4小时）、白细胞介素-1β和白细胞介素-6（6小时）分泌的影响。采用蛋白质免疫印迹分析研究SPMG对Tat诱导的蛋白激酶Cζ、蛋白激酶Cθ和蛋白激酶Cσ磷酸化的影响。
SPMG（50至100微克×毫升-1）显著抑制Tat激活的THP-1细胞中肿瘤坏死因子α、白细胞介素-1β和白细胞介素-6的分泌。在THP-1细胞中，Tat刺激后蛋白激酶Cζ、蛋白激酶Cθ和蛋白激酶Cσ的磷酸化水平显著升高，而只有蛋白激酶Cσ的磷酸化水平受到SPMG（50至100微克×毫升-1）的抑制。
SPMG可能通过抑制蛋白激酶Cσ的激活来抑制THP-1细胞中促炎细胞因子的分泌。
