Parasitol Res. 2008 Feb 28 [Epub ahead of print]
Toxoplasma gondii induces prostaglandin E(2) synthesis in macrophages via signal pathways for calcium-dependent arachidonic acid production and PKC-dependent induction of cyclooxygenase-2
Peng BW, Lin JY, Zhang T
Medical College of Wuhan University, Wuhan, Hubei Province, 430071, People’s Republic of China.
In this study, the intracellular signaling pathway of PGE(2) synthesis in macrophages (RAW264.7) induced by Toxoplasma gondii was investigated. The T. gondii-induced PGE(2) production in macrophages increased in a time-dependent manner, as PGE(2) induction began at 4 h, peaked at 12 h, and then plateaued at a high level. COX-2 mRNA in macrophages was detectable as early as 4 h after treatment; the maximal expression was observed at 8 h. The earliest induction of COX-2 protein occurred at 4 h and peaked at 16 h; meanwhile, COX-1 mRNA level and protein production remained unchanged throughout. Indomethacin and nimesulide inhibited tachyzoite-induced PGE(2) production and COX-2 mRNA expression in macrophages but they had no significant effect on COX-2 protein expression. EGTA, TFP and BAPTA/AM inhibited both arachidonic acid (AA) and PGE(2) production without effecting COX-2 protein expression, but verapamil inhibited neither AA nor PGE(2) production. H7 was found to inhibit PGE(2) production, and COX-2 mRNA expression and protein expression by tachyzoite or LPS stimulated macrophages in a dose-dependent manner. Our results demonstrate that T. gondii induces PGE(2) biosynthesis in RAW264.7 macrophages by regulating AA production through a calcium-dependent pathway and induction of COX-2 expression by a PKC-dependent pathway.
PMID: 18305957 [PubMed - as supplied by publisher]