IEX-1 suppresses apoptotic damage in human intestinal epithelial Caco-2 cells induced by co-culturing with macrophage-like THP-1 cells.
We have reported previously that apoptosis of intestinal epithelial Caco-2 cells is induced by co-culturing with human macrophage-like THP-1 cells, mainly via the action of TNFα (tumour necrosis factor α) secreted from THP-1 cells [Satsu, Ishimoto, Nakano, Mochizuki, Iwanaga and Shimizu (2006) Exp. Cell Res. 312, 3909-3919]. Our recent DNA microarray analysis of co-cultured Caco-2 cells showed that IEX-1 (immediate early-response gene X-1) is the most significantly increased gene during co-culture [Ishimoto, Nakai, Satsu, Totsuka and Shimizu (2010) Biosci. Biotechnol. Biochem. 74, 437-439]. Hence, we investigated the role of IEX-1 in the co-culture-induced damage of Caco-2 cells. We showed that IEX-1 expression induced in Caco-2 cells was suppressed by anti-TNFα antibody treatment. Experiments using IEX-1-overexpressing and -knockdown Caco-2 cells suggested that IEX-1 was involved in the suppression of Caco-2 cell damage. Increases in caspase 3 activity and TNFR1 (TNF receptor 1) mRNA expression were shown in IEX-1-knockdown Caco-2 cells, suggesting that IEX-1 plays a role in the suppression of apoptosis and protects cells by controlling sensitivity to TNFα under both normal and inflammatory conditions.
Department of Applied Biological Chemistry, Graduate school of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. sabuyoko43@hotmail.com
Yoko
Y
Ishimoto
Hideo
H
Satsu
Mamoru
M
Totsuka
Makoto
M
Shimizu
D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D018938:Caco-2 Cells; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019610:Cytoprotection / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha