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NF‐κB Activation Pathway is Essential for the Chemokine Expression in Intestinal Epithelial Cells Stimulated with Clostridium difficile Toxin A
Author(s) -
Kim J. M.,
Lee J. Y.,
Yoon Y. M.,
Oh Y.K.,
Youn J.,
Kim Y.J.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.001756.x
Subject(s) - clostridium difficile toxin a , clostridium difficile toxin b , chemokine , downregulation and upregulation , nf κb , toxin , iκbα , interleukin 8 , biology , microbiology and biotechnology , iκb kinase , inflammation , signal transduction , cancer research , clostridium difficile , immunology , gene , biochemistry , antibiotics
Intestinal epithelial cells are known to upregulate the expression of several chemokines in response to stimulation with bacterial toxin. However, the cellular mechanisms of Clostridium difficile toxin A‐induced mucosal inflammation have not yet been fully elucidated. In this study, we investigated whether nuclear factor‐kappa B (NF‐κB) could regulate chemokine expression in intestinal epithelial cells. Toxin A increased the levels of NF‐κB complexes containing p65/p50 heterodimers and p65/p65 homodimers. Concurrently, toxin A decreased the levels of IκBα. Toxin A stimulation also increased the signals of phosphorylated IκB kinase (IKK)α/β and NF‐κB‐inducing kinase (NIK). In the toxin A‐stimulated HT‐29 cells, the suppression of IKK or NIK inhibited the upregulation of downstream target genes of NF‐κB such as IL‐8 and monocyte‐chemotactic protein (MCP)‐1 and similarly, inhibition of NF‐κB also downregulated the expression of IL‐8, growth‐related oncogene‐α, and MCP‐1. These results suggest that NF‐κB signalling events may be involved in the inflammatory responses to toxin A produced by toxigenic C. difficile .