[Effect of sulfated polymannuroguluronate on Tat induced proinflammatory cytokines release in THP-1 cells and its mechanism of action].
OBJECTIVE
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.


METHODS
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.


RESULTS
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)).


CONCLUSIONS
SPMG suppresses the secretion of proinflammatory cytokines in THP-1 cells may be by inhibiting PKCsigma activation.
Hui
Bin
B
Marine Drug and Food Institute, Ocean University of China, Qingdao, China.
Geng
Mei-yu
MY
Li
Jing
J
D045744:Cell Line, Tumor; D015696:Gene Products, tat / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D010766:Phosphorylation; D011134:Polysaccharides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D000074121:Protein Kinase C-theta; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D015696:Gene Products, tat; D053583:Interleukin-1beta; D015850:Interleukin-6; D007527:Isoenzymes; D011134:Polysaccharides; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000074121:Protein Kinase C-theta; D014409:Tumor Necrosis Factor-alpha; D000099221:Protein Kinase C zeta; C489185:sulfated polymannuroguluronate; C076233:PRKCQ protein, human