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-1α significantly enhanced T84 short- circuit current (I(sc)) responsiveness to secretagogues in comparison to SEMF not activated by IL-1α. The sensitivity of T84 cell I(sc) to Ca²⁺- dependent, but not adenosine 3',5'-cyclic monophosphate-dependent, secretagogues was augmented by IL-1α-treated SEMF. These effects of IL-1α are directly correlated with SEMF prostaglandin E₂ (PGE₂) production. Both IL-1α augmentation of Cl^- secretagogue responsiveness and PGE₂ formation were inhibited by IL-1 receptor antagonist. Within 5 h, IL-1α 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-1α accentuates intestinal SEMF augmentation of enterocyte responsiveness to Ca²⁺-dependent Cl^- secretagogues. PGE₂ is an important mediator of SEMF-enterocyte interaction. The effects of IL-1α on SEMF PGE₂ productions are, at least in part, due to stimulation of COX gene expression.