Comparative Study of Vanadate- and Phorbol Ester-induced Cyclo-oxygenase-2 Expression in Human Endothelial Cells

Summary

Our previous study showed that vanadate, an inhibitor of protein tyrosine phosphatases, induced the expression of cyclo-oxygenase (COX)-2 in a protein-tyrosine-kinase (PTK)-dependent manner in human umbilical vein endothelial cells (HUVEC). Here, we further compared the actions of vanadate and phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), on induction of COX-2 with special reference to mitogen-activated protein kinases (MAPKs) in HUVEC. Vanadate induced activation of three families of MAPKs, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun amino-terminal kinase (JNK) 1, while activation of ERK1/2 alone was induced by PMA. The former activation by vanadate and the latter one by PMA were inhibited by tyrphostin-47, an inhibitor of PTKs, and by Ro31-8220, a PKC inhibitor, respectively. Either tyrphostin-47, PD98059, a specific inhibitor of the upstream kinase toward ERK1/2, or SB203580, a specific inhibitor of p38, completely suppressed vanadate-induction of COX-2 mRNA and protein. On the other hand, PMA-induction of COX-2 mRNA and protein was abolished by Ro31-8220 or PD98059 but not by SB203580. These data indicate that PMA-induced and PKC-dependent expression of COX-2 requires mainly activation of ERK1/2 among MAPKs, while activation of both ERK1/2 and p38 or possibly of all three families of MAPKs is necessary for vanadate-induced and PTK-dependent expression of COX-2.

Key words

Cyclo-oxygenase - protein-tyrosine-kinase - protein kinase C - mitogen-activated protein kinase

• References

• 1 Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta 1996; 1299: 125-40.
• 2 Habib A, Créminon C, Frobert Y, Grassi J, Pradelles P, Maclouf J. Demonstration of an inducible cyclooxygenase in human endothelial cells using antibodies raised against the carboxyl-terminal region of the cyclooxygenase-2. J Biol Chem 1993; 268: 23448-54.
• 3 Moncada S, Higgs EA, Vane JR. Human arterial and venous tissues generate prostacyclin (prostaglandin X), a potent inihibitor of platelet aggregation. Lancet 1997; 1: 18-20.
• 4 Wu KK, Hatzakis H, Lo SS, Seong DC, Sanduja SK, Tai HH. Stimulation of de novo synthesis of prostaglandin G/H synthase in human endothelial cells by phorbol ester. J Biol Chem 1988; 263: 19043-7.
• 5 Chanmugam P, Feng L, Liou S, Jang BC, Boudreau M, Yu G, Lee JH, Kwon HJ, Beppu T, Yoshida M, Xia Y, Wilson CB, Hwang D. Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis. J Biol Chem 1995; 270: 5418-26.
• 6 Blanco A, Habib A, Levy-Toledano S, Maclouf J. Involvement of tyrosine kinases in the induction of cyclo-oxygenase-2 in human endothelial cells. Biochem J 1995; 312: 419-23.
• 7 Hirai K, Takayama H, Tomo K, Okuma M. Protein-tyrosine-kinase-dependent expression of cyclo-oxygenase-1 and -2 mRNAs in human endothelial cells. Biochem J 1997; 322: 373-7.
• 8 Waskiewicz AJ, Cooper JA. Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr Opin in Cell Biol 1995; 7: 798-805.
• 9 Cano E, Mahadevan LC. Parallel signal processing among MAPKs. Trends Biochem Sci 1995; 20: 117-22.
• 10 Xie W, Herschman HR. v-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor. J Biol Chem 1995; 270: 27622-8.
• 11 Xie W, Herschman HR. Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J Biol Chem 1996; 271: 31742-8.
• 12 Guan Z, Baier LD, Morrison AR. p38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E₂ biosynthesis stimulated by interleukin-1β. J Biol Chem 1997; 272: 8083-9.
• 13 Guan Z, Buckman SY, Miller BW, Springer LD, Morrison AR. Interleukin-1β-induced cyclooxygenase-2 expression requires activation of both c-Jun NH₂-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. J Biol Chem 1998; 273: 28670-6.
• 14 Ridley SH, Sarsfield SJ, Lee JC, Bigg HF, Cawston TE, Taylor DJ, DeWitt DL, Saklatvala J. Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase. J Immunol 1997; 158: 3165-73.
• 15 Pouliot M, Baillargeon J, Lee JC, Cleland LG, James MJ. Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated human monocytes by inhibitors of p38 mitogen-activated protein kinase. J Immunol 1997; 158: 4930-7.
• 16 Ridley SH, Dean JLE, Sarsfield SJ, Brook M, Clark AR, Saklatvala J. A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA. FEBS Lett 1998; 439: 75-80.
• 17 Subbaramaiah K, Chung WJ, Dannenberg AJ. Ceramide regulates the transcription of cyclooxygenase-2. J Biol Chem 1998; 273: 32943-9.
• 18 Moriguchi T, Toyoshima F, Masuyama N, Hanafusa H, Gotoh Y, Nishida E. A novel SPAK/JNK kinase, MKK7, stimulated by TNFα and cellular stresses. EMBO J 1997; 16: 7045-53.
• 19 Moriguchi T, Kuroyanagi N, Yamaguchi K, Gotoh Y, Irie K, Kano T, Shirakabe K, Muro Y, Shibuya H, Matsumoto K, Nishida E, Hagiwara M. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem 1996; 271: 13675-9.
• 20 Shimizu H, Takayama H, Lee J-D, Satake K, Taniguchi T, Yamamura H, Nakamura T. Effects of vanadate on prostacyclin and endothelin-1 production and protein-tyrosine phosphorylation in human endothelial cells. Thromb Haemost 1994; 72: 973-8.
• 21 Ezumi Y, Takayama H, Okuma M. Differential regulation of protein-tyrosine phosphatases by integrin α_IIbβ₃ through cytoskeletal reorganization and tyrosine phosphorylation in human platelets. J Biol Chem 1995; 270: 11927-34.
• 22 Takayama H, Kroll MH, Gimbrone Jr MA, Schafer AI. Turnover of eicosanoid precursor fatty acids among phospholipid classes and sub-classes of cultured human umbilical vein endothelial cells. Biochem J 1989; 258: 427-34.
• 23 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156-9.
• 24 Gilliland G, Perkin S, Blanchard K, Bunn HF. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci USA 1990; 87: 2725-9.
• 25 Celi FS, Zenilman ME, Shuldiner AR. A rapid and versatile method to synthesize internal standards for competitive PCR. Nucleic Acids Res 1993; 21: 1047.
• 26 Ichinohe T, Takayama H, Ezumi Y, Yanagi S, Yamamura H, Okuma M. Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI. J Biol Chem 1995; 270: 28029-36.
• 27 Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR. PD098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem 1995; 270: 27489-94.
• 28 Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC. SB203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 1995; 364: 229-33.
• 29 Huot J, Houle F, Marceau F, Landry J. Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ Res 1997; 80: 383-92.
• 30 Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D, Hunt T, Nebreda AR. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heart shock proteins. Cell 1994; 78: 1027-37.
• 31 Freshney NW, Rawlinson L, Guesdon F, Jones E, Cowley S, Hsuan J, Saklatvala J. Interleukin-I activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell 1994; 78: 1039-49.
• 32 Jackson BA, Goldstein RH, Roy R, Cozzani M, Taylor L, Polgar P. Effects of transforming growth factor β and interleukin-1β on expression of cyclooxygenase 1 and 2 and phospholipase A₂ mRNA in lung fibroblasts and endothelial cells in culture. Biochem Biophys Res Commun 1993; 197: 1465-74.
• 33 Hwang D, Jang BC, Yu G, Boudreau M. Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide: mediation through both mitogen-activated protein kinase and NF-κB signaling pathways in macrophages. Biochem Pharmacol 1997; 54: 87-96.
• 34 Modur V, Zimmerman GA, Prescott SM, McIntyre TM. Endothelial cell inflammatory responses to tumor necrosis factor α. J Biol Chem 1996; 271: 13094-102.
• 35 Zyglewska T, Wu L-C, Xu X-M, Conlan MG, Wang L-H, Wu KK. Quantitative analysis of vascular prostaglandin H synthase mRNA levels by competitive polymerase chain reaction. J Lab Clin Med 1993; 122: 542-8.
• 36 Schmedtje JF, Ji Jr Y-S, Liu W-L, DuBois RN, Runge MS. Hypoxia induces cyclooxygenase-2 via the NF-kB p65 transcription factor in human vascular endothelial cells. J Biol Chem 1997; 72: 601-8.
• 37 Brown K, Park S, Kanno T, Franzoso G, Siebenlist U. Mutual regulation of the transcriptional activator NF-kB and its inhibitor, Ik B-α. Proc Natl Acad Sci USA 1993; 90: 2532-6.
• 38 Sun SC, Ganchi PA, Ballard DW, Greene WC. NF-κB controls expression of inhibitor IκB-α: Evidence for an inducible autoregulatory pathway. Science 1993; 259: 1912-5.
• 39 O’Neill LAJ. Towards an understanding of the signal transduction pathways for interleukin 1. Biochim Biophys Acta 1995; 1266: 31-44.
• 40 Goppelt-Struebe M, Hahn A, Stroebel M, Reiser COA. Independent regulation of cyclo-oxygenase 2 expression by p42/44 mitogen-activated protein kinases and Ca²⁺/calmodulin-dependent kinase. Biochem J 1999; 339: 329-34.
• 41 Fournier T, Fadok V, Henson PM. Tumor necrosis factor-α inversely regulates prostaglandin D₂ and prostaglandin E₂ production in murine macrophages – Synergistic action of cyclic AMP on cyclooxygenase-2 expression and prostaglandin E₂ synthesis. J Biol Chem 1997; 272: 31065-72.