Macrophage migration inhibitory factor contributes to development of nonsteroidal anti-inflammatory drugs-induced gastric injury in mice.

Macrophage migration inhibitory factor (MIF) plays an important role in the development of inflammation. In this study, we evaluated the role of MIF in gastric injury induced by non-steroidal anti-inflammatory drugs (NSAIDs) in mice. To induce gastric injury, mice were intraperitnoneally injected with 35 mg/kg of indomethacin. The level of MIF protein was up-regulated and severe gastric injury with inflammatory infiltrate was observed in the stomach of wild-type (WT) mice treated with indomethacin. The severity of gastric injury in MIF-deficient mice was less than that in WT mice. Increase in TNF-α in gastric tissue of mice treated with indomethacin was suppressed in MIF-deficient mice. The expression of HSP70, which has a cytoprotective role, was remarkably up-regulated in the stomach of MIF-deficient mice compared with WT mice after indomethacin treatment. Our results suggest that MIF is essential for the development of gastric injury-induced by NSAIDs.