THE EFFECTS OF TRINITROBENZENE SULFONIC-ACID (TNB) ON COLONOCYTE ARACHIDONIC-ACID METABOLISM

In previous studies we found that luminal perfusion of the isolated le ft colon of the rabbit with the hapten, trinitrobenzene, resulted in t he production of an acute inflammatory process associated with alterat ions in eicosanoid metabolism. As the colitis was attenuated by cycloo xygenase inhibitors it is possible that the inflammation was mediated by arachidonic acid metabolites. In the present study it was intended to evaluate the effect of trinitrobenzene on eicosanoid metabolism in transformed human colonic cells by exposing Caco-2 cells to various do ses of trinitrobenzene. Cell injury was evaluated by measuring lactate dehydrogenase levels and cyclooxygenase and lipoxygenase activity was evaluated by measuring prostanoid and leukotriene production. In sepa rate experiments resting and trinitrobenzene stimulated cells were tre ated with indomethacin and dexamethasone. Trinitrobenzene produced inc reased prostaglandin E2 and g-keto prostaglandin F-1 alpha and increas ed lactate dehydrogenase levels. Leukotriene B-4 was significantly inc reased compared to control values at the highest TNB concentration adm inistered. Indomethacin inhibited the lactate dehydrogenase and prosta noid changes, suggesting that the inflammatory changes produced were m ediated by the prostanoids. Dexamethasone administered for 1 hr prior to trinitrobenzene decreased the g-keto prostaglandin F1 alpha but did not alter trinitrobenzene-produced changes in lactate dehydrogenase c oncentrations. Exposure of Caco-2 cells to dexamethasone for 24 hr dec reased the trinitrobenaene produced lactate dehydrogenase and eicosano id changes. The results suggest that trinitrobenzene produces an acute injury to Caco-2 cells that may be mediated by the cyclooxygenase enz ymes. (C) 1996 Academic Press, Inc.