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 |
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Rok vydání: | 2005 |
Předmět: |
Cholera Toxin
medicine.medical_treatment Immunology Gene Expression Biology medicine.disease_cause Permeability Microbiology Interferon-gamma chemistry.chemical_compound Immune system Adjuvants Immunologic Interferon Cell Line Tumor Virology polycyclic compounds medicine Humans Intestinal Mucosa Tumor necrosis factor α Interleukin-6 Tumor Necrosis Factor-alpha Interleukin-8 Cholera toxin NF-kappa B Drug Synergism NF-κB Cell Biology biochemical phenomena metabolism and nutrition Intercellular Adhesion Molecule-1 bacterial infections and mycoses Up-Regulation Protein Subunits chemistry Adjuvant Signal Transduction medicine.drug |
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 |
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