| Autor: |
Murakami, Makoto, Kuwata, Hiroshi, Amakasu, Yoshihisa, Shimbara, Satoko, Nakatani, Yoshihito, Atsumi, Gen-ichi, Kudo, Ichiro |
| Zdroj: |
Journal of Biological Chemistry; August 1997, Vol. 272 Issue: 32 p19891-19897, 7p |
| Abstrakt: |
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 PGE2generation by this cell line in response to interleukin (IL)-1β and tumor necrosis factor α (TNFα) was dependent upon cytosolic phospholipase A2(cPLA2) and cyclooxygenase (COX)-2. Expression of these two enzymes was reduced by cPLA2or COX-2 inhibitors and restored by adding exogenous arachidonic acid or PGE2, indicating that PGE2produced by these cells acted as an autocrine amplifier of delayed PGE2generation through enhanced cPLA2and COX-2 expression. Exogenous addition or enforced expression of type IIA sPLA2significantly increased IL-1β/TNFα-initiated PGE2generation, which was accompanied by increased expression of both cPLA2and COX-2 and suppressed by inhibitors of these enzymes. Thus, our results revealed a particular cross-talk between the two PLA2enzymes and COX-2 for delayed PGE2biosynthesis by a type IIA sPLA2-deficient cell line. cPLA2is responsible for initiating COX-2-dependent delayed PGE2generation, and sPLA2, if introduced, enhances PGE2generation by increasing cPLA2and COX-2 expression via endogenous PGE2. |
| Databáze: |
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