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

15-Deoxy-Delta (12,14) prostaglandin J(2) and interleukin-4 are endogenous anti-inflammatory substances. In this study, we examined the effects of 15- deoxy-Delta (12,14) prostaglandin J(2) and interleukin-4 in glial cells fro m the Toll-like receptor-4-mutant (C3H/HeJ) and wild-type (C3H/HeN) mouse b rains. The lipopolysaccharide-induced expression of inducible nitric oxide (NO) synthase acid cyclooxygenase-2 in the Toll-like receptor-4-mutant glia l cells have significantly lower levels (about half and quarter, respective ly) than those in the wild-type cells. Treatment with both interleukin-4 (a t 10 ng/ml, for 48 h) and 15-deoxy-Delta (12,14) prostaglandin J(2) (at 3 m uM, for 30 min) completely inhibited the lipopolysaccharide-induced express ion of inducible NO synthase and cyclooxygenase-2. In contrast, heme oxygen ase-1 was induced by 15-deoxy-Delta (12,14) prostaglandin J(2) alone, but w as not changed by interleukin-4, or lipopolysaccharide. The inhibitory prot ein of nuclear factor-kappaB was degraded by lipopolysaccharide in both mut ant and wild-type glial cells, and this degradation was not inhibited by ei ther 15-deoxy-Delta (12,14) prostaglandin J(2) or interteukin-4. These resu lts suggest that the response to lipopolysaccharide is partially dependent on Toll-like receptor-4 in mouse glial cells, and that 15-deoxy-Delta (12,1 4) prostaglandin J(2) and interleukin-4 differently regulate the expression of inducible NO synthase and cyclooxygenase-2, and heme oxygenase-1. (C) 2 001 Elsevier Science B.V. All rights reserved.