Effects of cholera toxin on macrophage production of co-stimulatory cytokines.
Cholera toxin (CT), the enterotoxin of Vibrio cholerae, is a potent mucosal and systemic immunogen and adjuvant. The precise mechanism of the adjuvanticity of CT is poorly understood. Our previous work has showed that CT up-regulates B7.2, but not B7.1 expression on macrophages, and thus increases their co-stimulatory activity. In the current study, the effects of CT on macrophage co-stimulatory cytokine production were investigated. Bone marrow macrophages were generated by culturing bone marrow cells with macrophage colony-stimulating factor. CT treatment increased endotoxin-stimulated macrophage IL-10, IL-6, and IL-1beta production, whereas it decreased IL-12, TNF-alpha and nitric oxide production. Antibody blocking experiments showed that CT inhibition of IL-12 and TNF-alpha production was mediated by increased IL-10 production, in that addition of anti-IL-10 monoclonal antibody abrogated CT inhibition. The decrease in nitric oxide production was in turn secondary to inhibition of TNF-alpha production. Taken together, our study demonstrated that CT has differential effects on various macrophage co-stimulatory cytokines, effects that are likely to contribute to its adjuvanticity.
Cong
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Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, Birmingham, USA.
Oliver
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Elson
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D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D002772:Cholera Toxin