Effects of 15-deoxy-Δ 12,14 prostaglandin J 2 and interluekin-4 in Toll-like receptor-4-mutant glial cells

Abstract

15-Deoxy-Δ 12,14 prostaglandin J 2 and interleukin-4 are endogenous anti-inflammatory substances. In this study, we examined the effects of 15-deoxy-Δ 12,14 prostaglandin J 2 and interleukin-4 in glial cells from the Toll-like receptor-4-mutant (C3H/HeJ) and wild-type (C3H/HeN) mouse brains. The lipopolysaccharide-induced expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2 in the Toll-like receptor-4-mutant glial cells have significantly lower levels (about half and quarter, respectively) than those in the wild-type cells. Treatment with both interleukin-4 (at 10 ng/ml, for 48 h) and 15-deoxy-Δ 12,14 prostaglandin J 2 (at 3 μM, for 30 min) completely inhibited the lipopolysaccharide-induced expression of inducible NO synthase and cyclooxygenase-2. In contrast, heme oxygenase-1 was induced by 15-deoxy-Δ 12,14 prostaglandin J 2 alone, but was not changed by interleukin-4 or lipopolysaccharide. The inhibitory protein of nuclear factor-κB was degraded by lipopolysaccharide in both mutant and wild-type glial cells, and this degradation was not inhibited by either 15-deoxy-Δ 12,14 prostaglandin J 2 or interleukin-4. These results suggest that the response to lipopolysaccharide is partially dependent on Toll-like receptor-4 in mouse glial cells, and that 15-deoxy-Δ 12,14 prostaglandin J 2 and interleukin-4 differently regulate the expression of inducible NO synthase and cyclooxygenase-2, and heme oxygenase-1.