INTERLEUKIN-1-BETA INDUCES CYTOSOLIC PHOSPHOLIPASE A(2) AND PROSTAGLANDIN-H SYNTHASE IN RHEUMATOID SYNOVIAL FIBROBLASTS - EVIDENCE FOR THEIR ROLES IN THE PRODUCTION OF PROSTAGLANDIN E(2)

被引:117
作者
HULKOWER, KI
WERTHEIMER, SJ
LEVIN, W
COFFEY, JW
ANDERSON, CM
CHEN, T
DEWITT, DL
CROWL, RM
HOPE, WC
MORGAN, DW
机构
[1] ABBOTT LABS, ABBOTT PK, IL 60064 USA
[2] HOFFMANN LA ROCHE INC, NUTLEY, NJ 07110 USA
[3] MICHIGAN STATE UNIV, E LANSING, MI 48824 USA
来源
ARTHRITIS AND RHEUMATISM | 1994年 / 37卷 / 05期
关键词
D O I
10.1002/art.1780370508
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. In order to investigate potential regulatory mechanisms for the increased production of prostaglandin E(2) (PGE(2)) in interleukin-1 beta (IL-1 beta)-stimulated rheumatoid synovial fibroblasts (RSF), this study examined the induction of phospholipase A(2) (PLA(2)) and prostaglandin H synthase (PGHS) enzymes and the correlation of these events with PGE(2) production in IL-1 beta-stimulated RSF. Methods. Protein and messenger RNA (mRNA) levels of cytosolic PLA(2) (cPLA(2)) and PGHS-2 enzymes in IL-1 beta-stimulated RSF were measured by Western and Northern blotting, respectively, using specific antisera and complementary DNA probes. Enzymatic activity of cPLA(2) was determined in cell-free reaction mixtures utilizing mixed micelles of C-14-phosphatidylcholine and Triton X-100 as the substrate. PGE(2) levels were quantitated using a commercial enzyme immunoassay kit. Results. Incubation of RSF with IL-1 beta increased the mRNA and protein levels for the high molecular weight cPLA(2) as well as for the mitogen/growth factor-responsive PGHS (PGHS-2). The IL-1 receptor antagonist completely abolished the induction of these two enzymes and the stimulation of PGE, production by IL-1 beta in RSF. In contrast, levels of the other known forms of these enzymes, i.e., the 14-kd secretory group II PLA(2) (sPLA(2)) and the constitutive form of PGHS (PGHS-1), were unaffected by IL-1 beta treatment. Conclusion. These are the first data to demonstrate the coordinate induction by IL-1 of cPLA(2) and PGHS-2 in RSF. The time-course for the induction of these enzymes suggests that their increase contributes to the increased production of PGE, in IL-1-treated RSF, and may help explain the capacity of RSF to produce large amounts of PGE(2).
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页码:653 / 661
页数:9
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