Prostaglandin E2 upregulates cyclooxygenase-2 expression in lipopolysaccharide-stimulated RAW 264.7 macrophages

被引:95
作者
Hinz, B [1 ]
Brune, K [1 ]
Pahl, A [1 ]
机构
[1] Univ Erlangen Nurnberg, Dept Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany
关键词
cyclooxygenase-2; prostaglandin E-2; cAMP; feedback regulation;
D O I
10.1006/bbrc.2000.2859
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Prostaglandin E-2 (PGE(2)) has been implicated in the regulation of inflammatory and immunological events. Using RAW 264.7 macrophages, the present study investigates the influence of PGE(2) on the expression of cyclooxygenase-2 (COX-2). Incubation of cells with PGE(2) increased lipopolysaccharide (LPS)-induced COX-2 mRNA levels in a concentration-dependent manner. Upregulation of COX-2 expression by PGE(2) was completely abolished by the specific adenylyl cyclase inhibitor 2',5'-dideoxyadenosine and mimicked by butaprost, a selective agonist of the adenylyl cyclase-coupled PGE(2) receptor subtype 2 (EP2), or 11-deoxy PGE(1), an EP2/EP4 receptor agonist. By contrast, the EP3/EP1 receptor agonists 17-phenyl-omega-trinor PGE(2) and sulprostone left LPS-induced COX-2 expression virtually unaltered. Upregulation of LPS-induced COX-2 expression and subsequent PGE(2) synthesis was also observed in the presence of the cell-permeable cAMP analogue dibutyryl cAMP and the adenylyl cyclase activator cholera toxin. Together, our data demonstrate that PGE(2) potentiates COX-2 mRNA expression via an adenylyl cyclase/cAMP-dependent pathway. In conclusion, upregulation of COX-2 expression via an autocrine feed-forward loop may in part contribute to the well-known capacity of PGE(2)/cAMP to modulate inflammatory processes. (C) 2000 Academic Press.
引用
收藏
页码:744 / 748
页数:5
相关论文
共 32 条
[1]  
Appleton I, 1996, Adv Pharmacol, V35, P27, DOI 10.1016/S1054-3589(08)60274-4
[2]   Prostanoid receptors of murine NIH 3T3 and RAW 264.7 cells - Structure and expression of the murine prostaglandin EP4 receptor gene [J].
Arakawa, T ;
Laneuville, O ;
Miller, CA ;
Lakkides, KM ;
Wingerd, BA ;
DeWitt, DL ;
Smith, WL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (47) :29569-29575
[3]  
BAILLY S, 1990, Cytokine, V2, P205, DOI 10.1016/1043-4666(90)90017-N
[4]  
BRUNE K, 1999, FAST FACTS RHEUMATOL, P18
[5]  
COLEMAN RA, 1994, PHARMACOL REV, V46, P205
[6]   Prostaglandins prevent inducible nitric oxide synthase protein expression by inhibiting nuclear factor-κB activation in J774 macrophages [J].
D'Acquisto, F ;
Sautebin, L ;
Iuvone, T ;
Di Rosa, M ;
Carnuccio, R .
FEBS LETTERS, 1998, 440 (1-2) :76-80
[7]   PROSTAGLANDIN ENDOPEROXIDE SYNTHASE - REGULATION OF ENZYME EXPRESSION [J].
DEWITT, DL .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1083 (02) :121-134
[8]   The triterpenoid quinonemethide pristimerin inhibits induction of inducible nitric oxide synthase in murine macrophages [J].
Dirsch, VM ;
Kiemer, AK ;
Wagner, H ;
Vollmar, AM .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 336 (2-3) :211-217
[9]   REGULATION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE (CYCLOOXYGENASE) ISOZYME EXPRESSION [J].
GOPPELTSTRUEBE, M .
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 1995, 52 (04) :213-222
[10]   Prostaglandin synthase 2 [J].
Herschman, HR .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1996, 1299 (01) :125-140