AIMTo 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.

METHODSThe 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.

RESULTSSPMG (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)).

CONCLUSIONSPMG suppresses the secretion of proinflammatory cytokines in THP-1 cells may be by inhibiting PKCsigma activation.

Cell Line, Tumor ; Gene Products, tat ; pharmacology ; Humans ; Interleukin-1beta ; secretion ; Interleukin-6 ; secretion ; Isoenzymes ; metabolism ; Phosphorylation ; Polysaccharides ; pharmacology ; Protein Kinase C ; metabolism ; Protein Kinase C-delta ; metabolism ; Protein Kinase C-theta ; Tumor Necrosis Factor-alpha ; secretion

Adolescent ; Adult ; Anemia, Aplastic ; blood ; Case-Control Studies ; Female ; Humans ; Isoenzymes ; metabolism ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Protein Kinase C ; metabolism ; Protein Kinase C-theta ; T-Lymphocytes, Cytotoxic ; cytology ; Th1 Cells ; cytology ; Young Adult