Effects of 15-deoxy-delta(12,14) prostaglandin J(2) and interleukin-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 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-Delta(12,14) prostaglandin J(2) (at 3 microM, 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-Delta(12,14) prostaglandin J(2) alone, but was not changed by interleukin-4 or lipopolysaccharide. The inhibitory protein of nuclear factor-kappa B was degraded by lipopolysaccharide in both mutant and wild-type glial cells, and this degradation was not inhibited by either 15-deoxy-Delta(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-Delta(12,14) prostaglandin J(2) and interleukin-4 differently regulate the expression of inducible NO synthase and cyclooxygenase-2, and heme oxygenase-1.
Kitamura
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan. yo-kita@mb.kyoto-phu.ac.jp
Kakimura
J
J
Koike
H
H
Umeki
M
M
Gebicke-Haerter
P J
PJ
Nomura
Y
Y
Taniguchi
T
T
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D015151:Immunoblotting; D007155:Immunologic Factors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D009457:Neuroglia / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D019948:Receptors, Interleukin-4 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D006360:Heat-Shock Proteins; D007155:Immunologic Factors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D006419:Heme Oxygenase (Decyclizing); D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2