RAT GASTRIC-MUCOSAL CELLS EXPRESS ICAM-1 AND PROINFLAMMATORY CYTOKINES DURING INDOMETHACIN-INDUCED MUCOSAL INJURY

Adhesion molecules and cytokines are known to be involved in the forma tion of acute gastric mucosal injury However, it Is not clear whether the gastric mucosal cells express these molecules and modulate the inf lammation. To clarify whether gastric mucosal cells express intercellu lar adhesion molecule-1 (ICAM-1) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1-alpha), a nd cytokine-induced neutrophil chemoattractant-2-beta (CINC-2-beta)) i n the formation of gastric mucosal injury, we have used rat indomethac in-induced gastric mucosal lesions as an in vivo model. The gene expre ssion of all cytokines and ICAM-1 increases at the early stages of ind omethacin-induced gastritis (TNF-alpha and IL-1-alpha gene expression began to increase earlier than that of ICAM-1 and CINC-2-beta) and can mainly be detected in the gastric epithelial layer. To further identi fy the source of those molecules, the epithelial cells were separated into seven fractions according to their sizes by a counterflow elution . ICAM-1 and CINC-2-beta gene expressions are particularly enhanced in the middle-sized cell fractions that are rich in gastric mucous-produ cing cells. The effect of TNF-alpha or IL-1-alpha on the gene expressi on of ICAM-1 and cytokines was examined by using RGM-1 cells as a mode l for gastric mucosal cells. RGM-1 cells show an augmented ICAM-1 and proinflammatory cytokine expression in response to TNF-alpha or IL-1-a lpha stimulation. Moreover, immunohistochemical staining also reveals an increase in ICAM-1 and CINC protein production in RGM-1 cells in re sponse to TNF-alpha stimulation. We conclude that gastric mucosal cell s express various cytokines and an adhesion molecule during the format ion of acute gastric mucosal injury and that they may modulate the inf lammation.