Prostaglandin E2 and Krüppel-like transcription factors synergistically induce the expression of decay-accelerating factor in intestinal epithelial cells.
The decay-accelerating factor (DAF) prevents the intestinal mucosa from bystander killing by complement. Prostaglandin E(2) (PGE(2)) induces the expression of DAF that may protect the tumour environment from complement attack. In the present study, we demonstrate synergistic actions of PGE(2) and two Krüppel-like factors (KLFs), which are zinc finger-containing transcription factors, in DAF regulation. Overexpression of KLF4 and KLF5 robustly induced transcriptional activity of the DAF promoter. In combination, PGE(2) and either KLF4 or KLF5 increased the expression of DAF in a synergistic fashion. Moreover, cyclooxygenase (COX-1 and COX-2) enzymes, KLF4/5 and DAF protein were coordinately expressed in normal intestinal mucosa as well as in intestinal neoplasm. In radiation-injured mouse intestine, COX-1 was rapidly induced and remained at relatively high levels. While KLF5 was quickly elevated after irradiation, KLF4 exhibited a delayed increase. Interestingly, levels of DAF increased gradually following the induction of COX-1 and KLFs. Mimicking the circumstances in vivo, coexpression of both COX and KLFs resulted in a synergistic or additive induction of DAF transcription in intestinal epithelial cells. Our data suggest that COX-derived PGE(2) may collaborate with KLF4/5 to regulate the activation of the complement system and exert diverse effects on the intestinal epithelium.
Shao
Jinyi
J
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Yang
Vincent W
VW
Sheng
Hongmiao
H
D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000276:immunology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000528:radiation effects; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011832:Radiation Injuries / Q000276:immunology; D014158:Transcription, Genetic
D018958:CD55 Antigens; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone