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Degradation of the Transcription Factors NF-kappaB, STAT3, and STAT5 Is Involved in Entamoeba histolytica-Induced Cell Death in Caco-2 Colonic Epithelial Cells
The Korean Journal of Parasitology ; : 459-469, 2014.
Article in English | WPRIM | ID: wpr-7401
ABSTRACT
Entamoeba histolytica is a tissue-invasive protozoan parasite causing dysentery in humans. During infection of colonic tissues, amoebic trophozoites are able to kill host cells via apoptosis or necrosis, both of which trigger IL-8-mediated acute inflammatory responses. However, the signaling pathways involved in host cell death induced by E. histolytica have not yet been fully defined. In this study, we examined whether calpain plays a role in the cleavage of pro-survival transcription factors during cell death of colonic epithelial cells, induced by live E. histolytica trophozoites. Incubation with amoebic trophozoites induced activation of m-calpain in a time- and dose-dependent manner. Moreover, incubation with amoebae resulted in marked degradation of STAT proteins (STAT3 and STAT5) and NF-kappaB (p65) in Caco-2 cells. However, IkappaB, an inhibitor of NF-kappaB, was not cleaved in Caco-2 cells following adherence of E. histolytica. Entamoeba-induced cleavage of STAT proteins and NF-kappaB was partially inhibited by pretreatment of cells with a cell-permeable calpain inhibitor, calpeptin. In contrast, E. histolytica did not induce cleavage of caspase-3 in Caco-2 cells. Furthermore, pretreatment of Caco-2 cells with a calpain inhibitor, calpeptin (but not the pan-caspase inhibitor, z-VAD-fmk) or m-calpain siRNA partially reduced Entamoeba-induced DNA fragmentation in Caco-2 cells. These results suggest that calpain plays an important role in E. histolytica-induced degradation of NF-kappaB and STATs in colonic epithelial cells, which ultimately accelerates cell death.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Calcium-Binding Proteins / Calpain / Signal Transduction / NF-kappa B / Cell Death / Colon / Caco-2 Cells / Caspases / I-kappa B Proteins / RNA, Small Interfering Limits: Humans Language: English Journal: The Korean Journal of Parasitology Year: 2014 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Calcium-Binding Proteins / Calpain / Signal Transduction / NF-kappa B / Cell Death / Colon / Caco-2 Cells / Caspases / I-kappa B Proteins / RNA, Small Interfering Limits: Humans Language: English Journal: The Korean Journal of Parasitology Year: 2014 Type: Article