Effect of sulfated polymannuroguluronate on Tat induced proinflammatory cytokines release in THP-1 cells and its mechanism of action.
- Author:
Bin HUI
1
;
Mei-yu GENG
;
Jing LI
Author Information
- Publication Type:Journal Article
- MeSH: 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
- From: Acta Pharmaceutica Sinica 2006;41(4):338-341
- CountryChina
- Language:Chinese
-
Abstract:
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.