Enprostil, a prostaglandin-E(2) analogue, inhibits interleukin-8 production of human colonic epithelial cell lines.
We previously reported that intracolonic administration of enprostil, a prostaglandin-E(2) (PGE(2)) analogue, had therapeutic effects on acute colitis induced in rodents by dextran sulfate sodium (DSS). In addition, production of growth-regulated gene product/cytokine-induced neutrophil chemoattractant-1 [GRO/CINC-1; an interleukin(IL)-8 like cytokine] was suppressed in the inflamed tissues. In the present study we used a human colon cancer cell line (HT-29) to investigate enprostil effects on the IL-8 production of intestinal epithelial cells stimulated by various stimulants. In a MTT assay, concentrations of enprostil >10(-5)M had cytotoxitic effects on HT-29 cells. Furthermore, 10(-6) M enprostil suppressed IL-8 production in HT-29 cells, SW620 and CaCo2 stimulated with interleukin-1 beta (IL-1 beta) or lipopolysaccharide (LPS), but did not suppress this response when cells were stimulated with tumour necrosis factor (TNF)-alpha. These results suggest that enprostil affects a point in the pathway between the IL-1 receptor or LPS receptor and nuclear factor-kappa B(NF-kappa B), without affecting the pathway between the TNF receptor and NF-kappa B, with the latter factor being required for the IL-8 gene transcription. The therapeutic effect of exogenous enprostil on DSS colitis may involve the inhibition of IL-8 production in colonic epithelial cells stimulated by IL-1 beta or LPS.
Toshina
K
K
Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
Hirata
I
I
Maemura
K
K
Sasaki
S
S
Murano
M
M
Nitta
M
M
Yamauchi
H
H
Nishikawa
T
T
Hamamoto
N
N
Katsu
K
K
D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology; D003106:Colon / Q000187:drug effects*; D000242:Cyclic AMP / Q000032:analysis; D015232:Dinoprostone / Q000031:analogs & derivatives*; D016620:Enprostil / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D016620:Enprostil; D015232:Dinoprostone