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Toxoplasma gondii induces prostaglandin E2 synthesis in macrophages via signal pathways for calcium-dependent arachidonic acid production and PKC-dependent induction of cyclooxygenase-2

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Abstract

In this study, the intracellular signaling pathway of PGE2 synthesis in macrophages (RAW264.7) induced by Toxoplasma gondii was investigated. The T. gondii-induced PGE2 production in macrophages increased in a time-dependent manner, as PGE2 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 PGE2 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 PGE2 production without effecting COX-2 protein expression, but verapamil inhibited neither AA nor PGE2 production. H7 was found to inhibit PGE2 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 PGE2 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.

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Acknowledgments

This work was supported by the funding of the National Ministry of Education No. 02074 and pivot program of the Department of Education in Fujian Province (No. JA02216).

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Authors and Affiliations

  1. Medical College of Wuhan University, Wuhan, Hubei Province, 430071, People’s Republic of China

    Bi-Wen Peng

  2. Department of Molecular Medicine, Fujian Medical University, Fuzhou, Fujian Province, 350004, People’s Republic of China

    Jian-yin Lin & Tao Zhang

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  1. Bi-Wen Peng
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  2. Jian-yin Lin
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Correspondence to Jian-yin Lin.

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Peng, BW., Lin, Jy. & Zhang, T. Toxoplasma gondii induces prostaglandin E2 synthesis in macrophages via signal pathways for calcium-dependent arachidonic acid production and PKC-dependent induction of cyclooxygenase-2. Parasitol Res 102, 1043–1050 (2008). https://doi.org/10.1007/s00436-007-0873-4

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  • DOI: https://doi.org/10.1007/s00436-007-0873-4

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