Cholera Toxin Potentiates Influences of IFN-γ Through Activation of NF-κB and Release of Tumor Necrosis Factor-α

Publisher Website
Google Scholar
Abstract
Cholera toxin (Ctx) is a potent adjuvant in the mucosal immune system. Previous studies have indicated that Ctx induces intestinal interferon-γ (IFN-γ) production and that adjuvant properties require activation of the IFN-γ receptor (IFNGR). Thus, we hypothesized that Ctx potentiates IFN-γ responses in intestinal epithelia. Initial studies suggested that Ctx enhances IFN-γ-mediated barrier disruption in cultured intestinal epithelia. This response was attributable to liberation of a soluble mediator into conditioned supernatants, subsequently identified as tumor necrosis factor-α (TNF-α). Extensions of these findings revealed that the Ctx A subunit induces transcriptional activation of proinflammatory genes in addition to TNF-α (interleukin-8 [IL- 8], intracellular adhesion molecule-1 [ICAM-1], and IL-6) and that such transactivation is mediated by the transcriptional regulator NF-κB. We conclude that Ctx elicits a proinflammatory phenotype in intestinal epithelia and that potentiation of IFN-γ-mediated barrier disruption by TNF-α may contribute to the overall adjuvant properties of Ctx.