Pyrimidinoceptor Potentiation of Macrophage PGE(2) Release Involved in the Induction of Nitric Oxide Synthase

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2000 Jun 24

PMID 10864883

Citations 10

Authors

B C Chen

W W Lin

Affiliations

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Abstract

We have previously demonstrated that Ca(2+)/calmodulin-dependent protein kinase (CaMK) mediates pyrimidinoceptor potentiation of LPS-elicited inducible nitric oxide synthase (iNOS) induction in murine J774 macrophages. In the present paper, we have explored the role of cyclo-oxygenase (COX)-dependent prostaglandin E(2) (PGE(2)) formation in this event. In J774 macrophages predominantly expressing P2Y(6) receptors, the simultaneous addition of UTP and lipopolysaccharide (LPS) resulted in potentiated increase in PGE(2) release. UTP-induced increased PGE(2) release was demonstrated by a concomitant increase in COX-2 protein expression, and was decreased by inhibitors specific for phosphatidylinositide-phospholipase C (PI-PLC), CaMK, protein kinase C (PKC), nuclear factor-kappa B (NF-kappaB) or COX-2. NS-398 (a selective COX-2 inhibitor) reduced LPS plus UTP-elicited iNOS induction and nitrite accumulation, supporting for the positive regulation of iNOS gene expression by endogenous PGE(2). Moreover, the cyclic AMP/PKA-dependent up-regulation of iNOS expression mediated by PGE(2) was drawn from the inhibitory effects of 2',5'-dideoxyadenosine, KT5720 and H-89. Exogenous PGE(2) induced NF-kappaB activation and potentiated nitrite accumulation in response to LPS. In addition to COX-2 induction, arachidonic acid (AA) release and steady-state mRNA levels of type V secretory phospholipase A(2) (sPLA(2)) and Ca(2+)-independent PLA(2) (iPLA(2)) were also increased in the presence of LPS and UTP; the LPS-induced increase in iPLA(2) activity was also potentiated by UTP. Taken together, we conclude that UTP-mediated COX-2 and iPLA(2) potentiation and PGE(2) formation contribute to the iNOS induction, and that CaMK activation is the primary step in the UTP enhancement of COX-2 induction.

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References

Lin W, Chen B, Hsu Y, Lee C, Shyue S . Modulation of inducible nitric oxide synthase induction by prostaglandin E2 in macrophages: distinct susceptibility in murine J774 and RAW 264.7 macrophages. Prostaglandins Other Lipid Mediat. 1999; 58(2-4):87-101. DOI: 10.1016/s0090-6980(99)00023-4. View

Kuroda A, Sugiyama E, Taki H, Mino T, Kobayashi M . Interleukin-4 inhibits the gene expression and biosyntheis of cytosolic phospholipase A2 in lipopolysaccharide stimulated U937 macrophage cell line and freshly prepared adherent rheumatoid synovial cells. Biochem Biophys Res Commun. 1997; 230(1):40-3. DOI: 10.1006/bbrc.1996.5885. View

Shirakawa F, Mizel S . In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol Cell Biol. 1989; 9(6):2424-30. PMC: 362315. DOI: 10.1128/mcb.9.6.2424-2430.1989. View

Moncada S, Palmer R, Higgs E . Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991; 43(2):109-42. View

Davis P, ELLIOTT L, Harris W, Hill C, Hurst S, Keech E . Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity. J Med Chem. 1992; 35(6):994-1001. DOI: 10.1021/jm00084a004. View

Blank V, Kourilsky P, Israel A . NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992; 17(4):135-40. DOI: 10.1016/0968-0004(92)90321-y. View

Norris J, Manley J . Selective nuclear transport of the Drosophila morphogen dorsal can be established by a signaling pathway involving the transmembrane protein Toll and protein kinase A. Genes Dev. 1992; 6(9):1654-67. DOI: 10.1101/gad.6.9.1654. View

Nathan C . Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992; 6(12):3051-64. View

Marotta P, Sautebin L, Di Rosa M . Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. Br J Pharmacol. 1992; 107(3):640-1. PMC: 1907741. DOI: 10.1111/j.1476-5381.1992.tb14499.x. View

10.

Martiny-Baron G, Kazanietz M, Mischak H, Blumberg P, Kochs G, Hug H . Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976. J Biol Chem. 1993; 268(13):9194-7. View

11.

Raddassi K, PETIT J, Lemaire G . LPS-induced activation of primed murine peritoneal macrophages is modulated by prostaglandins and cyclic nucleotides. Cell Immunol. 1993; 149(1):50-64. DOI: 10.1006/cimm.1993.1135. View

12.

Salvemini D, Misko T, Masferrer J, Seibert K, Currie M, NEEDLEMAN P . Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci U S A. 1993; 90(15):7240-4. PMC: 47112. DOI: 10.1073/pnas.90.15.7240. View

13.

Koide M, Kawahara Y, Nakayama I, Tsuda T, Yokoyama M . Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells. Synergism with the induction elicited by inflammatory cytokines. J Biol Chem. 1993; 268(33):24959-66. View

14.

Fujihara M, Connolly N, Ito N, Suzuki T . Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production. J Immunol. 1994; 152(4):1898-906. View

15.

Ackermann E, Kempner E, Dennis E . Ca(2+)-independent cytosolic phospholipase A2 from macrophage-like P388D1 cells. Isolation and characterization. J Biol Chem. 1994; 269(12):9227-33. View

16.

Eberhardt W, Kunz D, Pfeilschifter J . Pyrrolidine dithiocarbamate differentially affects interleukin 1 beta- and cAMP-induced nitric oxide synthase expression in rat renal mesangial cells. Biochem Biophys Res Commun. 1994; 200(1):163-70. DOI: 10.1006/bbrc.1994.1429. View

17.

Kunz D, Muhl H, Walker G, Pfeilschifter J . Two distinct signaling pathways trigger the expression of inducible nitric oxide synthase in rat renal mesangial cells. Proc Natl Acad Sci U S A. 1994; 91(12):5387-91. PMC: 44000. DOI: 10.1073/pnas.91.12.5387. View

18.

Tonetti M, Sturla L, Bistolfi T, Benatti U, De Flora A . Extracellular ATP potentiates nitric oxide synthase expression induced by lipopolysaccharide in RAW 264.7 murine macrophages. Biochem Biophys Res Commun. 1994; 203(1):430-5. DOI: 10.1006/bbrc.1994.2200. View

19.

Naumann M, Scheidereit C . Activation of NF-kappa B in vivo is regulated by multiple phosphorylations. EMBO J. 1994; 13(19):4597-607. PMC: 395392. DOI: 10.1002/j.1460-2075.1994.tb06781.x. View

20.

Tetsuka T, Daphna-Iken D, Srivastava S, Baier L, Dumaine J, Morrison A . Cross-talk between cyclooxygenase and nitric oxide pathways: prostaglandin E2 negatively modulates induction of nitric oxide synthase by interleukin 1. Proc Natl Acad Sci U S A. 1994; 91(25):12168-72. PMC: 45398. DOI: 10.1073/pnas.91.25.12168. View