title: NF-kappa B activation pathway is essential for the chemokine expression in intestinal epithelial cells stimulated with Clostridium difficile toxin A.
abstract: 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-kappaB) could regulate chemokine expression in intestinal epithelial cells. Toxin A increased the levels of NF-kappaB complexes containing p65/p50 heterodimers and p65/p65 homodimers. Concurrently, toxin A decreased the levels of IkappaBalpha. Toxin A stimulation also increased the signals of phosphorylated IkappaB kinase (IKK)alpha/beta and NF-kappaB-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-kappaB such as IL-8 and monocyte-chemotactic protein (MCP)-1 and similarly, inhibition of NF-kappaB also downregulated the expression of IL-8, growth-related oncogene-alpha, and MCP-1. These results suggest that NF-kappaB signalling events may be involved in the inflammatory responses to toxin A produced by toxigenic C. difficile.
authors.affiliation: Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea. jungmogg@hanyang.ac.kr
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Y M
authors.initials: YM
authors.lastname: Yoon
authors.forename: Y-K
authors.initials: YK
authors.lastname: Oh
authors.forename: J
authors.initials: J
authors.lastname: Youn
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001427:Bacterial Toxins; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016360:Clostridioides difficile / Q000276:immunology* / Q000472:pathogenicity; D004768:Enterotoxins / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D018925:Chemokines; D004768:Enterotoxins; D016328:NF-kappa B; C041348:tcdA protein, Clostridium difficile; D051550:I-kappa B Kinase