Effect of Pertussis Toxin and Herbimycin A on Proteinase-activated Receptor 2-mediated Cyclooxygenase 2 Expression in Helicobacter Pylori-infected Gastric Epithelial AGS Cells

Overview

Journal Yonsei Med J

Specialty General Medicine

Date 2011 Apr 14

PMID 21488197

Citations 4

Authors

Ji Hye Seo

Jeong Yeon Seo

Hae-Yun Chung

Hyeyoung Kim

Affiliations

Soon will be listed here.

Abstract

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of G(i) protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection.

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References

Boolbol S, Dannenberg A, Chadburn A, Martucci C, Guo X, Ramonetti J . Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res. 1996; 56(11):2556-60. View

LaMorte V, Harootunian A, Spiegel A, Tsien R, Feramisco J . Mediation of growth factor induced DNA synthesis and calcium mobilization by Gq and Gi2. J Cell Biol. 1993; 121(1):91-9. PMC: 2119771. DOI: 10.1083/jcb.121.1.91. View

Seo J, Kim K, Kim H . Role of proteinase-activated receptor-2 on cyclooxygenase-2 expression in H. pylori-infected gastric epithelial cells. Ann N Y Acad Sci. 2007; 1096:29-36. DOI: 10.1196/annals.1397.067. View

Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W . Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci U S A. 1994; 91(25):12013-7. PMC: 45366. DOI: 10.1073/pnas.91.25.12013. View

Li G, Han C, Xu L, Lim K, Isse K, Wu T . Cyclooxygenase-2 prevents fas-induced liver injury through up-regulation of epidermal growth factor receptor. Hepatology. 2009; 50(3):834-43. PMC: 2758493. DOI: 10.1002/hep.23052. View

Hsieh H, Tung W, Wu C, Wang H, Lin C, Wang T . Thrombin induces EGF receptor expression and cell proliferation via a PKC(delta)/c-Src-dependent pathway in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2009; 29(10):1594-601. DOI: 10.1161/ATVBAHA.109.185801. View

Yamaoka Y, Kodama T, Gutierrez O, Kim J, Kashima K, Graham D . Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol. 1999; 37(7):2274-9. PMC: 85136. DOI: 10.1128/JCM.37.7.2274-2279.1999. View

Kuipers E, Perez-Perez G, Meuwissen S, Blaser M . Helicobacter pylori and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst. 1995; 87(23):1777-80. DOI: 10.1093/jnci/87.23.1777. View

Yada K, Shibata K, Matsumoto T, Ohta M, Yokoyama S, Kitano S . Protease-activated receptor-2 regulates cell proliferation and enhances cyclooxygenase-2 mRNA expression in human pancreatic cancer cells. J Surg Oncol. 2005; 89(2):79-85. DOI: 10.1002/jso.20197. View

10.

Lee T, Jeon Y, Kim J, Park N, Kang S, Lee H . Lack of association of the cyclooxygenase-2 and inducible nitric oxide synthase gene polymorphism with risk of cervical cancer in Korean population. Ann N Y Acad Sci. 2007; 1095:134-42. DOI: 10.1196/annals.1397.017. View

11.

Goh F, Sloss C, Cunningham M, Nilsson M, Cadalbert L, Plevin R . G-protein-dependent and -independent pathways regulate proteinase-activated receptor-2 mediated p65 NFkappaB serine 536 phosphorylation in human keratinocytes. Cell Signal. 2008; 20(7):1267-74. DOI: 10.1016/j.cellsig.2008.02.015. View

12.

Cho S, Lim J, Kim K, Kim H . Involvement of Ras and AP-1 in Helicobacter pylori-induced expression of COX-2 and iNOS in gastric epithelial AGS cells. Dig Dis Sci. 2009; 55(4):988-96. DOI: 10.1007/s10620-009-0828-y. View

13.

Kamath L, Meydani A, Foss F, Kuliopulos A . Signaling from protease-activated receptor-1 inhibits migration and invasion of breast cancer cells. Cancer Res. 2001; 61(15):5933-40. View

14.

Hou L, Kapas S, Cruchley A, Macey M, Harriott P, Chinni C . Immunolocalization of protease-activated receptor-2 in skin: receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology. 1998; 94(3):356-62. PMC: 1364253. DOI: 10.1046/j.1365-2567.1998.00528.x. View

15.

Della Rocca G, Maudsley S, Daaka Y, Lefkowitz R, Luttrell L . Pleiotropic coupling of G protein-coupled receptors to the mitogen-activated protein kinase cascade. Role of focal adhesions and receptor tyrosine kinases. J Biol Chem. 1999; 274(20):13978-84. DOI: 10.1074/jbc.274.20.13978. View

16.

Tatsuguchi A, Sakamoto C, Wada K, Akamatsu T, Tsukui T, Miyake K . Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans. Gut. 2000; 46(6):782-9. PMC: 1756437. DOI: 10.1136/gut.46.6.782. View

17.

Seo M, Nam H, Kim S, Juhnn Y . Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-kappaB in H1299 human lung cancer cells. Biochem Biophys Res Commun. 2009; 381(2):153-8. DOI: 10.1016/j.bbrc.2009.01.188. View

18.

Hamilton J, Frauman A, Cocks T . Increased expression of protease-activated receptor-2 (PAR2) and PAR4 in human coronary artery by inflammatory stimuli unveils endothelium-dependent relaxations to PAR2 and PAR4 agonists. Circ Res. 2001; 89(1):92-8. DOI: 10.1161/hh1301.092661. View

19.

Moss J, Bruni P, Hsia J, Tsai S, Watkins P, Halpern J . Pertussis toxin-catalyzed ADP-ribosylation: effects on the coupling of inhibitory receptors to the adenylate cyclase system. J Recept Res. 1984; 4(1-6):459-74. DOI: 10.3109/10799898409042567. View

20.

Manukyan M, Nalbant P, Luxen S, Hahn K, Knaus U . RhoA GTPase activation by TLR2 and TLR3 ligands: connecting via Src to NF-kappa B. J Immunol. 2009; 182(6):3522-9. PMC: 2684960. DOI: 10.4049/jimmunol.0802280. View