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

Autor: Cormac T. Taylor, Richard S. Blumberg, Richard S. Pitman, Sean P. Colgan
Rok vydání: 2005
Předmět:
Zdroj: Journal of Interferon & Cytokine Research. 25:209-219
ISSN: 1557-7465
1079-9907
DOI: 10.1089/jir.2005.25.209
Popis: Cholera toxin (Ctx) is a potent adjuvant in the mucosal immune system. Previous studies have indicated that Ctx induces intestinal interferon-gamma (IFN-gamma) production and that adjuvant properties require activation of the IFN-gamma receptor (IFNGR). Thus, we hypothesized that Ctx potentiates IFN-gamma responses in intestinal epithelia. Initial studies suggested that Ctx enhances IFN-gamma-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-alpha (TNF-alpha). Extensions of these findings revealed that the Ctx A subunit induces transcriptional activation of proinflammatory genes in addition to TNF-alpha (interleukin-8 [IL- 8], intracellular adhesion molecule-1 [ICAM-1], and IL-6) and that such transactivation is mediated by the transcriptional regulator NF-kappaB. We conclude that Ctx elicits a proinflammatory phenotype in intestinal epithelia and that potentiation of IFN-gamma-mediated barrier disruption by TNF-alpha may contribute to the overall adjuvant properties of Ctx.
Databáze: OpenAIRE