PMID- 17113579 OWN - NLM STAT- MEDLINE DCOM- 20070405 LR - 20161124 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 556 IP - 1-3 DP - 2007 Feb 5 TI - Peroxisome proliferator-activated receptor alpha-independent effects of peroxisome proliferators on cysteinyl leukotriene production in mast cells. PG - 172-80 AB - The effects of peroxisome proliferators, the ligands of a nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha, on cysteinyl leukotriene production were investigated in rodent mast cells. Peroxisome proliferators Wy-14,643 (30 microM) and fenofibrate (100 microM) significantly inhibited the cysteinyl leukotriene production that was induced by antigen (Ag) treatment after overnight sensitization to Ag specific immunoglobulin E (IgE) in a rat basophilic leukemia (RBL)-2H3 mast cell line. Similar inhibition by these drugs was observed in IgE and Ag-treated mouse bone marrow-derived mast cells, A23187-treated RBL-2H3 and A23187-treated mouse peritoneal macrophages. Wy-14,643 (30 microM) and fenofibrate (100 microM) did not affect the release of radioactivity from RBL-2H3 pre-incubated with [(3)H]-arachidonic acid, which is considered an index of phospholipase A(2) activity. Wy-14,643 (30 microM) and fenofibrate (100 microM) did not directly inhibit 5-lipoxygenase activity. Troglitazone was found to directly inhibit the activity of 5-lipoxygenase. The PPARalpha mRNA level was at less than the limit of detection for the realtime polymerase chain reaction both in RBL-2H3 and bone marrow-derived mast cells. Wy-14,643 (30 microM) and fenofibrate (100 microM) did not induce acyl-CoA oxidase mRNA in RBL-2H3, which was reported to be induced by peroxisome proliferators via PPARalpha in hepatocytes. Wy-14,643 (30 microM) and fenofibrate (100 microM) inhibited the cysteinyl leukotriene production in bone marrow-derived mast cells from PPARalpha-null mice. It was concluded that the inhibitory effects of these peroxisome proliferators on cysteinyl leukotriene production are independent of PPARalpha in mast cells. FAU - Yamashita, Masamichi AU - Yamashita M AD - Department of Pathophysiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan. may@tohoku-pharm.ac.jp LA - eng PT - Journal Article DEP - 20061019 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Leukotrienes) RN - 0 (PPAR alpha) RN - 0 (Peroxisome Proliferators) RN - 0 (Pyrimidines) RN - 0 (cysteinyl-leukotriene) RN - 37341-29-0 (Immunoglobulin E) RN - 86C4MRT55A (pirinixic acid) RN - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase) RN - EC 1.3.3.6 (Acyl-CoA Oxidase) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.2.1.- (Hexosaminidases) RN - K848JZ4886 (Cysteine) RN - U202363UOS (Fenofibrate) SB - IM MH - Acyl-CoA Oxidase/metabolism MH - Animals MH - Arachidonate 5-Lipoxygenase/metabolism MH - Bone Marrow Cells/cytology/drug effects/metabolism MH - Cell Line, Tumor MH - Cells, Cultured MH - Cysteine/*biosynthesis MH - Fenofibrate/*pharmacology MH - Hexosaminidases/metabolism MH - Immunoglobulin E/metabolism MH - Leukotrienes/*biosynthesis MH - Macrophages, Peritoneal/cytology/drug effects/metabolism MH - Mast Cells/*drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - PPAR alpha/genetics/*physiology MH - Peroxisome Proliferators/*pharmacology MH - Phospholipases A/metabolism MH - Pyrimidines/*pharmacology MH - Rats EDAT- 2006/11/23 09:00 MHDA- 2007/04/06 09:00 CRDT- 2006/11/23 09:00 PHST- 2006/05/30 00:00 [received] PHST- 2006/10/06 00:00 [revised] PHST- 2006/10/10 00:00 [accepted] PHST- 2006/11/23 09:00 [pubmed] PHST- 2007/04/06 09:00 [medline] PHST- 2006/11/23 09:00 [entrez] AID - S0014-2999(06)01152-6 [pii] AID - 10.1016/j.ejphar.2006.10.032 [doi] PST - ppublish SO - Eur J Pharmacol. 2007 Feb 5;556(1-3):172-80. doi: 10.1016/j.ejphar.2006.10.032. Epub 2006 Oct 19.