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.
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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.
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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) |