IL-1β induction of NF-κB activation in human intestinal epithelial cells is independent of oxyradical signaling

Alexander A. Parikh, M. Ryan Moon, Timothy A. Pritts, Josef E. Fischer, Csaba Szabó, Per Olof Hasselgren, Andrew L. Salzman

    Research output: Contribution to journalArticle

    24 Scopus citations

    Abstract

    IL-1β stimulation of cultured epithelial cells induces the degradation of IκBα and the consequent nuclear translocation of NF-λB, a critical proinflammatory transcription factor in the mucosal host immune response. The role of reactive oxygen intermediates, serine protease activity, and tyrosine kinase activity in the activation of NF-κB is weakly conserved across various cell lineages and has not been defined in human enterocytes, a major target of oxidant stress in sepsis, thermal injury, and hemorrhagic shock. We report here that in Caco-2BBe cells, a transformed human colon cancer cell line with features of small intestinal epithelial cells in culture, exposure to oxidant stress (hydrogen peroxide 1-10 mM) did not induce NF-κB activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL-1β-induced IκBα degradation and NF-κB activation. Genistein, a non-specific tyrosine kinase inhibitor, also had no effect on IL-1β-mediated effects on NF-κB. Serine protease inhibition by tosyl-lysine-chloromethylketone and tosyl-phenylalanine-chloromethylketone inhibited IκBα degradation and NF-κB activation stimulated by IL-1β. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL-1β stimulation and NF-κB nuclear translocation.

    Original languageEnglish (US)
    Pages (from-to)8-13
    Number of pages6
    JournalShock
    Volume13
    Issue number1
    DOIs
    StatePublished - Jan 2000

      Fingerprint

    Keywords

    • Cytokines
    • Inflammation
    • Mucosa
    • Sepsis
    • Transcription factor

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

    Cite this

    Parikh, A. A., Moon, M. R., Pritts, T. A., Fischer, J. E., Szabó, C., Hasselgren, P. O., & Salzman, A. L. (2000). IL-1β induction of NF-κB activation in human intestinal epithelial cells is independent of oxyradical signaling. Shock, 13(1), 8-13. https://doi.org/10.1097/00024382-200013010-00002