Abstract
Increased mucosal apoptosis is seen in H.pylori-infected gastric tissue; however, the precisemechanism by which this organism triggers programmedcell death is poorly understood and is investigated in this study. One pathway for induction ofapoptosis is the Fas Ag pathway. Normal gastric andsmall bowel tissue express low levels of Fas antigen andnondetectable levels of Fas ligand. Consequent to H. pylori infection, The re is elevated expressionof Fas antigen in mucosal cells concurrent with Fasligand expressing lymphocytes. This prompted us toinvestigate the potential role of Fas in mediating H. pylori-related apoptosis. It has been shownthat inflammatory cytokines are abundant in H.pylori-infected tissue and that cytokines regulate theexpression of Fas Ag in various tissue types. Using cell culture, we examine The role of specificinflammatory cytokines in activating this pathway. Thiscommunication presents the first evidence to implicatethe Fas pathway in mediating apoptosis in H.pylori-associated gastric and duodenal ulcer disease.
Similar content being viewed by others
REFERENCES
Marshall BJ, Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lance t 1:1311-1315, 1984
Peek RM, Blaser MJ: Pathophysiology of Helicobacterpyloriinduced gastritis and peptic ulcer disease. Am J Med 102:200-207, 1997
Harris PR, Mobley HLT, Perez-Perez GI, Blaser MJ, Smith PD: Helicobacterpylori urease is a potent stimulus of mononucle ar phagocyte activation and in¯ ammatory cytokine production. Gastroenterology 111:419-425, 1996
Leake R: The cell cycle and regulation of cancer cell growth. Ann NY Acad Sci 784:252-262, 1996
Friedman RM, Grimley P, Baron S: Biological effects of the interferons and oTher cytokines. BioTherapy 8( 3-4):189-198, 1996
Oyaizu N, McCloskey TW, Than S, Hu R, Kalyanaraman VS, Pahwa S: Crosslinking of CD4 molecules upregulates Fas antigen expression in lymphocyte s by inducing interferon gamma and tumor necrosis factor-alpha se cre tion. Blood 84( 8):2622-2631, 1994
Tanaka M, Suda T, Takahashi T, Nagata S: expression of the functional soluble form of human Fas ligand in activated lymphocyte s. EMBOJ 14(6):1129-1135, 1995
French LE, Hahne M, Viard I, Radlgrube r G, Zanone R, Becker K, Muller C, Tschopp J: Fas and Fas ligand in embryos and adult mice: Ligand expression in se ve ral immuneprivileged tissues and co-expression in adult tissues characterized by apoptotic cell turnover. J Cell Bio 133( 2):335-343, 1996
Sharma SA, Tummuru MK, Miller GG, Blaser MJ: Interleukin-8 response of gastric epithelial cell lines to Helicobacterpylori stimulation in vitro. Infect Immun 63(5):1681-1687, 1995
Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, Imanishi J: Expression of cytokine mRNA in gastric mucosa with Hel icoba c ter pylori infe ct ion. Scand J Gas troenterol 30(12):1153-1159, 1995
Estaquier J, Tanaka M, Suda T, Nagata S, Goldstein P, Ameisen JC: Fas-mediated apoptosis of CD41 and CD81T cells from human immunode ficiency virus-infected persons: Differential in vitro preventive effects of cytokines and protease antagonists. Blood 87(12):4959-4966, 1996
Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Te sti R, Gassuzzo A: Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto' s thyroiditis. Science 275:960-963, 1997
Schroder JM, Sticherling M, Henneicke HH, Preissne r WC, Christophers E: IL-1 alpha or TNF alpha stimulates rele ase of three NAP-1/IL-8 related neutrophil chemotactic proteins in human dermal fi broblasts. J Immunol 144:2223-2232, 1990
Oyaizu N, McCloskey TW, Than S, Puhwa S: Inhibition of CD4 crosslinking induced lymphocytes apoptosis by vesnarinone as a nove l immunomodulating agent: Vesnarinone inhibits Fas expression and apoptosis by blocking cytokine se cretion. Blood 87(6):2361-2368, 1996
Ni R, Tomita Y, Matsuda K, Ichihara A, Ishimura K, Ogasawara J, Nagata S: Fas mediated apoptosis in primary cultured rat hepatocytes. Exp Cell Res 215:332-337, 1994
Houghton J, Korah RM, Kim KH, Small MB: A role for apoptosis in the pathogenesis of AIDS-related idiopathic esophage al ulcers. J Infect Dis 175:1216-1219, 1997
French LE, Tschopp J: Constitutive Fas ligand expression in several non-lymphoid mouse tissues: Implications for immune protection and cell turnover. Behring Inst Miett 97:156-160, 1996
Hubbard-Smith K, Patsalis P, Pardinas JR, Jha KK, Henderson AS, Oze r HL: Altered chromosome 6 in immortal human fibroblasts. Mol Cell Biol 12:2273-2281, 1992
Ishida M, Gomyo Y, Tate be S, Ohfuji S, Ito H: Apoptosis in human gastric mucosa, chronic gastritis, dysplasia and caraacinoma: Analysis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labe ling. Virchows Arch 428( 4-5):229-235, 1996
Hall PA, Coates PJ, Ansari B, Hopwood D: Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis. J Cell Sci 107:3569-3577, 1994
Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege.Science 270:1189-1192, 1995
Bellgrau D, Gold D, Selawry H, More J, Franzusoff A, Duke R: A role for CD95 ligand in preventing graft re jection. Nature 377:630-632, 1995
Moss SF, Calam J, Agarwal B, Wang S, Holt PR: Induction of gastric epithelial apoptosis by Helicobacterpylori. Gut 38:498-]501, 1996
Li H, Mellgard B, Helander HF: Inoculation of VacA 2 and CagA2 Helicobacterpylori delays gastric ulcer healing in The rat. Scand J Gastroenterol 32(5):439-444, 1997
Piotrowski J, Piotrowski E, Skrodzka D, Slomiany A, Slomiany BL: Induction of acute gastritis and epithelial apoptosis by Helicobacterpylori lipopolysaccharide. Scand J Gastroenterol 32(3):203-211, 1997
Piotrowski J, Skrodzka D, Slomiany A, Slomiany BL: Helicobacterpylori lipopolysaccharide induces gastric epithelial cells apoptosis. Biochem Mol Biol Int 40(3):597-602, 1996
Hayashi H, Tatebe S, Osaki M, Goto A, Suzuki Y, Ito H: Expression of Fas Ag and its mediation of apoptosis in human gastric cell lines. Jpn J Cancer Res 88(1):49-55, 1997
Nagata S: Fas mediated apoptosis. Adv Exp Med Biol 406:119-124, 1996
Chang K, Fujiwara Y, Wyle P, Tarnawski A: Helicobacterpylori toxin inhibits growth and proliferation of cultured gastric cellsÐ KATO III. J Physiol Pharmacol 44( 1):17-22, 1993
Rights and permissions
About this article
Cite this article
Houghton, J., Korah, R.M., Condon, M.R. et al. Apoptosis in Helicobacterpylori-Associated Gastric and Duodenal Ulcer Disease Is Mediated via the Fas Antigen Pathway. Dig Dis Sci 44, 465–478 (1999). https://doi.org/10.1023/A:1026628601284
Issue Date:
DOI: https://doi.org/10.1023/A:1026628601284