Dextran sulfate sodium-induced colitis is associated with enhanced low molecular mass polypeptide 2 (LMP2) expression and is attenuated in LMP2 knockout mice.

Abstract

Low molecular mass polypeptide 2 (LMP2) is an inducible proteasome subunit. Our goals were to examine LMP2 expression in mice with dextran sulfate sodium (DSS)-induced colitis and to evaluate colitis in LMP2 knockout (LMP2-/-) mice. Mice were given 2.5% DSS in the drinking water. On day 0, 2, 4, or 6 after DSS treatment, LMP2 expression was determined in the distal colon by western blot and immunohistochemistry. Parameters of colitis were measured in LMP2-/- mice or wild-type mice. LMP2 expression was enhanced in the colon of DSS-treated mice at all time points. Symptoms of DSS-induced colitis were always lower in LMP2-/- mice. Normalized histology scores and colonic IL-1ss levels increased over the 6-day study period in wild-type mice. These parameters were significantly reduced in LMP2-/- mice that consumed DSS for 6 days. Enhanced LMP2 expression contributes to the pathogenesis of DSS-induced colitis in mice.