d-609 and prolinedithiocarbamate

Secretion of Monocyte Chemotactic Protein-1 (MCP-1) by fibroblasts infected with Toxoplasma gondii was studied in vitro. A significantly higher MCP-1 secretion was observed 24 h after infection by live tachyzoites. Analysis of chemokine mRNA transcripts by RNase protection assay revealed that this MCP-1 secretion seems associated with increased MCP-1 mRNA expression. However, these increased levels of MCP-1 secretion and expression were not obtained after stimulation by heat-killed tachyzoites or parasites pre-treated by a specific inhibitor of phosphatidylcholine-specific phospholipase C (D609). Inhibition of parasite multiplication by pyrimethamine did not modify MCP-1 secretion. Thus, it appeared that the active penetration of T. gondii in cells was of major importance in the induction of MCP-1 secretion. None of the other chemokines studied by RNase protection assay (lymphotactin, RANTES, IP-10, MIP-1alpha, MIP-1beta, IL-8, and I-309) were expressed after infection by live tachyzoites. We also found that MCP-1 secretion induced by live T. gondii is blocked by inhibitors of nuclear factor (NF)-kappaB activation, ALLN and MG132. Such data indicate that NF-kappaB could be involved in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute to the recruitment of monocytes and lymphocytes and thus participate in the control of T. gondii infection and in its pathogenesis.

Topics: Animals; Antiprotozoal Agents; Bridged-Ring Compounds; Cells, Cultured; Chemokine CCL2; Chemokines; Enzyme Inhibitors; Fibroblasts; Gene Expression Regulation; Humans; Kinetics; Leupeptins; Mice; Norbornanes; Proline; Pyrimethamine; Thiocarbamates; Thiones; Time Factors; Toxoplasma; Transcription, Genetic; Type C Phospholipases