Entamoeba histolytica modulates TNF-alpha, IL-1 alpha/beta and c-fos gene expression in macrophages.
E. histolytica infections induce a state of transient suppression of cell-mediated immunity. As macrophages are involved in host defense in amebiasis, we determined whether soluble amebic lysates (Eh) can modulate TNF-alpha, IL-1 alpha/beta and c-fos gene expression in naive bone marrow-derived macrophages (BM delta). By Northern analysis, the RNA production of these genes after 0, 0.5, 1 and 3 h exposure to Eh was determined and compared to lipopolysaccharide (LPS) stimulation. In response to Eh, TNF-alpha mRNA was increased two fold while IL-1 alpha/beta RNA levels were increased 6- and 19-fold, respectively. Pretreatment of BM delta with H7, a PKC inhibitor, abrogated Eh induced TNF-delta gene expression and reduced IL-1 alpha/beta gene expression 3.5- to 4-fold over control levels. We conclude that E. histolytica stimulates BM delta to induce TNF-alpha gene expression through a PKC-dependent pathway and IL-1 alpha/beta gene expression partially through PKC and another yet undetermined pathway(s).
Seguin
R
R
Institute of Parasitology, McGill University, Ste. Anne-de-Bellevue, P.Q., Canada.
Chadee
K
K
D000818:Animals; D001854:Bone Marrow Cells; D002457:Cell Extracts / Q000494:pharmacology; D004748:Entamoeba histolytica / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D002457:Cell Extracts; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha