Clostridium difficile Toxin A Upregulates Bak Expression through PGE2 Pathway in Human Colonocytes.
J Microbiol Biotechnol
; 29(10): 1675-1681, 2019 Oct 28.
Article
em En
| MEDLINE
| ID: mdl-31474101
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 (PGE2) produced in response to toxin A stimulation. However, the molecular mechanism by which PGE2 mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, PGE2-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 PGE2 production, and further showed that this effect was recapitulated by an EP1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves PGE2-upregulation of Bak through the EP1 receptor.
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MEDLINE
Assunto principal:
Toxinas Bacterianas
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Dinoprostona
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Clostridioides difficile
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Enterotoxinas
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Proteína Killer-Antagonista Homóloga a bcl-2
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Mucosa Intestinal
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article