title: Escherichia coli induces apoptosis in human monocytic U937 cells through the Fas/FasL signaling pathway.
abstract: Apoptosis is a genetically regulated cellular suicide mechanism that plays an essential role in development and in defense of multicellular organism. Escherichia coli (E. coli) can induce monocyte apoptosis; however, the mechanism is not clear. This study determines if Fas/FasL regulates E. coli-induced human monocyte line U937 cell apoptosis. We found that infection of U937 cells with E. coli induced rapid cell death in a dose- and time-dependent manner displaying the characteristic features of apoptosis. Moreover, opsonized E. coli induced U937 apoptosis with a higher apoptotic rate (53.29 ± 5.83%) than non-opsonized E. coli (19.37 ± 2.56%). Studying the underlying mechanisms we found that the E. coli-induced apoptosis was associated with a more prominent induction expression of Fas/FasL in a time- and dose-dependent manner. Furthermore, E. coli treatment resulted in a significant increase in the levels of DR5, TRAIL, and FADD, but exerted no statistically significant effects on the levels of DR4. The activity of caspase-8 enzyme increased in infection groups, positively correlated with apoptosis rate. Taken together, these results clearly indicate that receptor-mediated phagocytosis of E. coli induces apoptosis. Moreover, our findings suggest a possible regulatory role of Fas/FasL in the pathway of E. coli infection.
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. wangjh1@sj-hospital.org
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Peng
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Yang
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Wang
authors.forename: Bao-Gang
authors.initials: BG
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006690:Bisbenzimidazole / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D061945:Caspase Inhibitors; D004926:Escherichia coli / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology*; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D009895:Opsonin Proteins; D011480:Protease Inhibitors; D053218:Receptors, Death Domain; D019014:fas Receptor; D053181:Caspase 8; D006690:Bisbenzimidazole