Evidence for protein kinase C pathway in the response of human peripheral blood mononuclear cells to cholera toxin

Cellular Immunology
T Krakauer

Abstract

Cholera toxin (CT) is a potent mucosal adjuvant and is widely used for vaccine studies in animal models. However, there have been few studies that describe the immunomodulating effects of CT on cells of the human immune system. In this study, the immunomodulatory properties of CT on human peripheral blood mononuclear cells (PBMC) were examined to gain insights to its effects on cells of the human immune system. CT induced production of immunostimulating (IL-1 beta and IL-6) and immunosuppressive (IL-10) cytokines by PBMC. However, the dose-response curve of its cytokine-inducing activity did not correlate well with the concentrations of intracellular cAMP generated by varying doses of CT. the CT mode of action on human PBMC, regarding induction of these cytokines, was clarified by the use of inhibitors of adenyl cyclase, protein kinase A (PKA), and protein kinase C (PKC). 2',3'-Dideoxyadenosine, which inhibits adenyl cyclase activity, reduced IL-1, IL-6, and IL-10 levels by 29, 15, and 28% respectively. HA1004, an inhibitor of PKA, reduced the IL-1 and IL-6 levels by 29 and 27%, respectively. The PKC inhibitor, H7, completely blocked the induction of all three cytokines by CT, suggesting a cAMP-independent mode of action for CT...Continue Reading

Citations

Nov 15, 2001·Animal Health Research Reviews·D L Foss, M P Murtaugh
Jun 20, 2002·Veterinary Immunology and Immunopathology·Michael P Murtaugh, Dennis L Foss
Feb 26, 2015·Wilderness & Environmental Medicine·Jon KrakauerJonathan Southard
Jan 7, 1999·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·P F PolliceR J O'Keefe

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