IL-1 stimulates intestinal myofibroblast COX gene expression and augments activation of Cl- secretion in T84 cells.
Because interleukin-1 (IL-1) is an important mediator in the inflamed intestine, its effects on enterocyte-subepithelial myofibroblast (SEMF) interaction were investigated in vitro. Acutely juxtaposing T84 cells with 18Co or P2JF SEMF preincubated with IL-1 alpha significantly enhanced T84 short-circuit current (Isc) responsiveness to secretagogues in comparison to SEMF not activated by IL-1 alpha. The sensitivity of T84 cell Isc to Ca(2+)-dependent, but not adenosine 3',5'-cyclic monophosphate-dependent, secretagogues was augmented by IL-1 alpha-treated SEMF. These effects of IL-1 alpha are directly correlated with SEMF prostaglandin E2 (PGE2) production. Both IL-1 alpha augmentation of Cl secretagogue responsiveness and PGE2 formation were inhibited by IL-1 receptor antagonist. Within 5 h, IL-1 alpha stimulated a 10-fold increase in cyclooxygenase (COX)-2 steady-state mRNA levels in 18Co cells. In contrast, COX-1 message levels increased more slowly to two- to threefold above control levels after 24 h incubation. These results demonstrate that the proinflammatory cytokine IL-1 alpha accentuates intestinal SEMF augmentation of enterocyte responsiveness to Ca(2+)-dependent CI-secretagogues. PGE2 is an important mediator of SEMF-enterocyte interaction. The effects of IL-1 alpha on SEMF PGE2 productions are, at least in part, due to stimulation of COX gene expression.
Hinterleitner
T A
TA
Medizinische Klinik, Karl-Franzens-Universität, Graz, Austria.
Saada
J I
JI
Berschneider
H M
HM
Powell
D W
DW
Valentich
J D
JD
D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology; D015232:Dinoprostone / Q000096:biosynthesis*; D004553:Electric Conductivity; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007583:Jejunum / Q000166:cytology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D002712:Chlorides; D007375:Interleukin-1; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone