1. NF-kappa B activation pathway is essential for the chemokine expression in intestinal epithelial cells stimulated with Clostridium difficile toxin A.
- Author
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Kim JM, Lee JY, Yoon YM, Oh YK, Youn J, and Kim YJ
- Subjects
- Amino Acid Sequence, Bacterial Toxins, Chemokines genetics, Chemokines metabolism, Clostridioides difficile pathogenicity, HT29 Cells, Humans, I-kappa B Kinase metabolism, Intestinal Mucosa cytology, Intestinal Mucosa enzymology, Molecular Sequence Data, NF-kappa B metabolism, Phosphorylation, Reverse Transcriptase Polymerase Chain Reaction, Chemokines biosynthesis, Clostridioides difficile immunology, Enterotoxins physiology, Intestinal Mucosa metabolism, NF-kappa B physiology, Signal Transduction immunology
- 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.
- Published
- 2006
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