Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Clostridium difficile Toxin A Inhibits Erythropoietin Receptor-Mediated Colonocyte Focal Adhesion Through Inactivation of Janus Kinase-2

  • Nam, Seung Taek (Department of Life Science, College of Natural Science, Daejin University) ;
  • Seok, Heon (Department of Biomedical Science, Jungwon University) ;
  • Kim, Dae Hong (Department of Life Science, College of Natural Science, Daejin University) ;
  • Nam, Hyo Jung (Department of Life Science, College of Natural Science, Daejin University) ;
  • Kang, Jin Ku (Department of Life Science, College of Natural Science, Daejin University) ;
  • Eom, Jang Hyun (Department of Life Science, College of Natural Science, Daejin University) ;
  • Lee, Min Bum (Department of Life Science, College of Natural Science, Daejin University) ;
  • Kim, Sung Kuk (Department of Life Science, College of Natural Science, Daejin University) ;
  • Park, Mi Jung (Department of Life Science, College of Natural Science, Daejin University) ;
  • Chang, Jong Soo (Department of Life Science, College of Natural Science, Daejin University) ;
  • Ha, Eun-Mi (College of Pharmacy, Catholic University of Daegu) ;
  • Shong, Ko Eun (Department of Animal Science and Biotechnology, Chungnam National University) ;
  • Hwang, Jae Sam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Kim, Ho (Department of Life Science, College of Natural Science, Daejin University)
  • Received : 2012.07.27
  • Accepted : 2012.08.01
  • Published : 2012.12.28
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Abstract

Previously, we demonstrated that the erythropoietin receptor (EpoR) is present on fibroblasts, where it regulates focal contact. Here, we assessed whether this action of EpoR is involved in the reduced cell adhesion observed in colonocytes exposed to Clostridium difficile toxin A. EpoR was present and functionally active in cells of the human colonic epithelial cell line HT29 and epithelial cells of human colon tissues. Toxin A significantly decreased activating phosphorylations of EpoR and its downstream signaling molecules JAK-2 (Janus kinase 2) and STAT5 (signal transducer and activator of transcription 5). In vitro kinase assays confirmed that toxin A inhibited JAK 2 kinase activity. Pharmacological inhibition of JAK2 (with AG490) abrogated activating phosphorylations of EpoR and also decreased focal contacts in association with inactivation of paxillin, an essential focal adhesion molecule. In addition, AG490 treatment significantly decreased expression of occludin (a tight junction molecule) and tight junction levels. Taken together, these data suggest that inhibition of JAK2 by toxin A in colonocytes causes inactivation of EpoR, thereby enhancing the inhibition of focal contact formation and loss of tight junctions known to be associated with the enzymatic activity of toxin A.

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References

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