Mitogen-activated protein kinase/I kappa B kinase/NF-kappa B-dependent and AP-1-independent CX3CL1 expression in intestinal epithelial cells stimulated with Clostridium difficile toxin A
- Title
- Mitogen-activated protein kinase/I kappa B kinase/NF-kappa B-dependent and AP-1-independent CX3CL1 expression in intestinal epithelial cells stimulated with Clostridium difficile toxin A
- Other Titles
- I kappa B kinase
- Author
- 김정목
- Keywords
- Clostridium difficiletoxin A; CX3CL1; Intestinal epithelial cells; Mitogen-activated protein kinase; Nuclear factor-kappaB
- Issue Date
- 2014-04
- Publisher
- Springer
- Citation
- JOURNAL OF MOLECULAR MEDICINE-JMM; APR 2014, 92, 4, p411-p427
- Abstract
- Clostridium difficile toxin A causes acute colitis associated with inflammatory cell infiltration and increased production of proinflammatory mediators. Although CX3CL1 (fractalkine) plays a role in chemoattracting monocytes/macrophages, NK cells, and T cells, little information is available on the regulated expression of CX3CL1 in response to toxin A stimulation. In this study, we investigated the role of C. difficile toxin A on CX3CL1 induction in intestinal epithelial cells. Stimulation of murine intestinal epithelial cells with toxin A resulted in the upregulation of CX3CL1. Expression of CX3CL1 was dependent on nuclear factor-kappaB (NF-kappa B) and I kappa B kinase (IKK) activation, while the suppression of activator protein-1 (AP-1) did not affect toxin A-induced CX3CL1 expression. Suppression of p38 mitogen-activated protein kinase (MAPK) significantly inhibited IKK-NF-kappa B signaling leading to CX3CL1 induction in C. difficile toxin A-stimulated cells. CX3CL1 was mainly secreted from the basolateral surfaces in toxin A-treated cells. Furthermore, inhibition of p38 activity attenuated the toxin A-induced upregulation of CX3CL1 in the mouse ileum in vivo. These results suggest that a pathway, including p38 MAPK, IKK, and NF-kappa B activation, is required for CX3CL1 induction in intestinal epithelial cells exposed to C. difficile toxin A and may regulate the development of intestinal inflammation induced by infection with toxigenic C. difficile. C. difficile toxin A causes colitis with inflammatory cell infiltration. CX3CL1 plays a role in chemoattracting immune cells. MAPK-NF-kappa B signaling is required for CX3CL1 induction in toxin A-exposed cells. CX3CL1 is mainly secreted from the basolateral surfaces. CX3CL1 may contribute to the regulation of toxigenic C. difficile infection.
- URI
- https://link.springer.com/article/10.1007/s00109-013-1117-yhttp://hdl.handle.net/20.500.11754/51666
- ISSN
- 0946-2716
- DOI
- 10.1007/s00109-013-1117-y
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > ETC
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