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Originally published In Press as doi:10.1074/jbc.M001250200 on May 1, 2000

J. Biol. Chem., Vol. 275, Issue 30, 22686-22694, July 28, 2000
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Induction of Secreted Type IIA Phospholipase A2 Gene Transcription by Interleukin-1beta
ROLE OF C/EBP FACTORS*

Charbel Massaad, Michel Paradon, Claire Jacques, Colette Salvat, Gilbert Bereziat, Francis Berenbaum, and Jean-Luc OlivierDagger

From UPRES-A CNRS 7079, UFR Saint Antoine, UPRES-A CNRS 7079, Université Pierre et Marie Curie, 7 quai Saint Bernard 75252 Paris Cedex 05, France

Secreted type IIA phospholipase A2, which is involved in arachidonic acid release, is abundantly produced by chondrocytes and secreted in the synovial fluids of patients affected by rheumatoid arthritis. Transfection experiments showed that interleukin-1beta stimulates the phospholipase A2 [-1614; +20] promoter activity by 6-7-fold and that the [-210; -176] fragment is critical for this stimulation. CAAT enhancer-binding protein (C/EBP) beta  and C/EBPdelta transcription factors bind to this element as shown by bandshift experiments. Interleukin-1beta increased the levels of C/EBPdelta mRNA as soon as 2 h and up to 24 h whithout affecting those of C/EBPbeta . Higher amounts of C/EBPdelta proteins correlate with the stimulation of C/EBPdelta mRNA. Mutations or 5' deletions in the upstream [-247; -210] region reduced by 2-fold the basal and interleukin-1beta -stimulated transcription activities. Two types of factors bind to overlapping sequences on this fragment: NF1-like proteins and the glucocorticoid receptor. The glucocorticoid receptor is responsible for a moderate stimulation of the promoter activity by dexamethasone and may interact with C/EBP factors to achieve a full transcription activity in basal conditions and in the presence of interleukin-1beta . A [-114; -85] proximal regulatory element forms three complexes in bandshift experiments, the slowest mobility one involving the Sp1 zinc finger factor. Mutation of this sequence reduced to 2-fold the stimulation of the promoter activity by interleukin-1beta or the C/EBP factors. Induction of the transcription of secreted type IIA phospholipase A2 gene by interleukin-1beta in chondrocytes absolutely requires C/EBPbeta and C/EBPdelta factors but does not involve NF-kappa B.

* This work was supported by the French Association pour la Recherche sur la Polyarthrite Rhumatoïde and the Société Française de Rhumatologie.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: UPRES-A CNRS 7079, Université Pierre et Marie Curie, 7 quai Saint Bernard 75252 Paris Cedex 05, France. Tel.: 33-1-44273256; Fax: 33-1-44275140; E-mail: olivier@ccr.jussieu.fr.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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