Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Clostridium difficile Toxin A Upregulates Bak Expression through PGE2 Pathway in Human Colonocytes

  • Kim, Young Ha (Division of Life Science and Chemistry, College of Natural Science, Daejin University) ;
  • Kim, Ho (Division of Life Science and Chemistry, College of Natural Science, Daejin University)
  • Received : 2019.06.17
  • Accepted : 2019.08.26
  • Published : 2019.10.28
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Abstract

Clostridium difficile toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 ($PGE_2$) produced in response to toxin A stimulation. However, the molecular mechanism by which $PGE_2$ mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, $PGE_2$-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on $PGE_2$ production, and further showed that this effect was recapitulated by an Prostaglandin E2(PGE2) receptor-1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves $PGE_2$-upregulation of Bak through the EP1 receptor.

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References

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