RRC ID 38996
著者 Murakami M, Kuwata H, Amakasu Y, Shimbara S, Nakatani Y, Atsumi G, Kudo I.
タイトル Prostaglandin E2 amplifies cytosolic phospholipase A2- and cyclooxygenase-2-dependent delayed prostaglandin E2 generation in mouse osteoblastic cells. Enhancement by secretory phospholipase A2.
ジャーナル J Biol Chem
Abstract We used the MC3T3-E1 cell line, which originates from C57BL/6J mouse that is genetically type IIA secretory phospholipase A2 (sPLA2)-deficient, to reveal the type IIA sPLA2-independent route of the prostanglandin (PG) biosynthetic pathway. Kinetic and pharmacological studies showed that delayed PGE2 generation by this cell line in response to interleukin (IL)-1beta and tumor necrosis factor alpha (TNFalpha) was dependent upon cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2. Expression of these two enzymes was reduced by cPLA2 or COX-2 inhibitors and restored by adding exogenous arachidonic acid or PGE2, indicating that PGE2 produced by these cells acted as an autocrine amplifier of delayed PGE2 generation through enhanced cPLA2 and COX-2 expression. Exogenous addition or enforced expression of type IIA sPLA2 significantly increased IL-1beta/TNFalpha-initiated PGE2 generation, which was accompanied by increased expression of both cPLA2 and COX-2 and suppressed by inhibitors of these enzymes. Thus, our results revealed a particular cross-talk between the two PLA2 enzymes and COX-2 for delayed PGE2 biosynthesis by a type IIA sPLA2-deficient cell line. cPLA2 is responsible for initiating COX-2-dependent delayed PGE2 generation, and sPLA2, if introduced, enhances PGE2 generation by increasing cPLA2 and COX-2 expression via endogenous PGE2.
巻・号 272(32)
ページ 19891-7
公開日 1997-8-8
DOI 10.1074/jbc.272.32.19891
PII S0021-9258(18)38866-5
PMID 9242654
MeSH Animals Cell Line Cyclooxygenase 1 Cyclooxygenase 2 Cytosol / drug effects Cytosol / enzymology Dinoprostone / metabolism* Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Interleukin-1 / pharmacology Isoenzymes / metabolism* Membrane Proteins Mice Mice, Inbred C57BL Osteoblasts / drug effects Osteoblasts / metabolism* Peroxidases / metabolism* Phospholipases A / metabolism* Phospholipases A2 Prostaglandin-Endoperoxide Synthases / metabolism* Tumor Necrosis Factor-alpha / pharmacology
IF 4.238
引用数 109
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)