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

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., TNFα, IL-1β and IL-6) and its related mechanism. MethodsThe effects of SPMG on Tat induced TNFα (4 h), IL-1β 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 PKCζ, PKCθ and PKCδ phosphorylation. ResultsSPMG (50 to 100 μg·mL^-1) markedly suppressed TNFα IL-1β and IL-6 secretion in Tat activated THP-1 cells. In THP-1 cells the phosphorylation levels of PKCζ, PKCθ and PKCδ significantly increased following Tat stimulation, and only PKCδ phosphorylation levels was inhibited by SPMG (50 to 100 μg·mL^-1). ConclusionSPMG suppresses the secretion of proinflammatory cytokines in THP-1 cells may be by inhibiting PKCδ activation.