Abstract
The mechanism of peptic ulcer recurrence is still unclear. Since ulcerogenic factors such as Helicobacter pylori, non-steroidal anti-inflammatory drugs and stress can increase expression of inflammatory cytokines in gastric mucosa, gastric mucosal inflammation may play key roles in ulcer recurrence. In acetic acid-induced gastric ulcers, persistent infiltration of neutrophils into scarred mucosa, which is caused by prostaglandin deficiency, affects future ulcer recurrence. In a rat model of ulcer recurrence which we developed, inflammatory cytokines such as interleukin (IL)-1β are key mediators of ulcer recurrence. In this model, IL-1β increases expression of adhesion molecules on both leukocytes and endothelial cells, and cytokines, leading to neutrophil infiltration into scarred mucosa. Gastric acid also plays important roles in recurrence of gastric ulcer in this model. Acid regulates inflammatory processes, including expression of adhesion molecules and inflammatory cytokines during ulcer recurrence. This review focuses on recent advances in understanding of the mechanisms underlying development of gastric ulcer recurrence.
Similar content being viewed by others
References
Andrews, F. J., Malcontenti-Wilson, C. and O'Brien, P. E. (1994). Effect of nonsteroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in gastric mucosa, Am. J. Physiol. 266, G657–G664.
Appleyard, C. B., McCafferty, D.-M., Tigley, A. W., et al. (1996). Tumor necrosis factor mediating of NSAIDs-induced gastric damage: role of leukocyte adherence, Am. J. Physiol. 27, G42–G48.
Arakawa, T., Satoh, H., Fukuda, T., et al. (1988). Gastric mucosal resistance and prostanoid levels after cimetidine treatment in rats, Digestion 41, 1–8.
Arakawa, T., Watanabe, T., Fukuda, T., et al. (1995). Rebamipide, a novel prostaglandin-inducer, accelerates healing and reduces recurrence of acetic acid-induced rat gastric ulcer: comparison with cimetidine, Dig. Dis. Sci. 40, 2469–2472.
Arakawa, T., Watanabe, T., Fukuda, T., et al. (1996). Indomethacin treatment during initial period of acetic acid-induced rat gastric ulcer healing promotes persistent polymorphonuclear cell-.300 T. Watanabe et al. infiltration and increases future ulcer recurrence: possible mediation of prostaglandins, Dig. Dis. Sci. 41, 2055–2061.
Beales, I. L. and Calam, J. (1997). Stimulation of IL-8 production in human gastric epithelial cells by Helicobacter pylori, IL-1beta and TNF-alpha requires tyrosine kinase activity, but not protein kinase C, Cytokine 9, 514–520.
Butcher, E. C. (1991). Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity, Cell 67, 1033–1036.
Crabtree, J. E., Shallcross, T. M., Heatley, R. V., et al. (1991). Mucosal tumour necrosis factor α and interleukin-6 in patients with Helicobacter pylori associated gastritis, Gut 32, 1473–1477.
Crabtree, J. E., Peichl, P., Wyatt, J. I., et al. (1993). Gastric interleukin-8 and IgA IL-8 autoantibody in H. pylori infection, Scand. J. Immunol. 37, 65–70.
Crabtree, J. E., Wyatt, J. I., Trejdosiewicz, L. K., et al. (1994). Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa, J. Clin. Pathol. 47, 61–66.
Diamond, M. S., Staunton, D. E., de Fougerolles, A. R., et al. (1990). ICAM-1 (CD54): A counter-receptor for Mac-1 (CD11b/ CD18), J. Cell Biol. 111, 3129–3139.
Enders, G., Brooks, W., von Jan, N., et al. (1995). Expression of adhesion molecules on human granulocytes after stimulation with Helicobactor pylori membrane proteins: Comparison with membrane proteins from other bacteria, Infect. Immun. 63, 2473–2477.
Fan, X. G., Chua, A., Fan, X. J., et al. (1995). Increased gastric production of interleukin-8 and tumour necrosis factor in patients with Helicobacter pylori infection, J. Clin. Pathol. 48, 133–136.
Graham, D. Y., Lew, G. M., Klein, P. D., et al. (1992). Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer: a randomized, controlled study, Ann. Intern. Med. 116, 705–708.
Gudmand-Høyer, E., Jensen, K. B., Krag, E., et al. (1978). Prophylactic effect of cimetidine in duodenal ulcer disease, Br. Med. J. 1, 1095–1097.
Hamaguchi, M., Watanabe, T., Higuchi, K., et al. (2001). Mechanisms and roles of neutrophil infiltration in stress-inducedgastric injury in rats, Dig. Dis. Sci. 46, 2708–2715.
Higuchi, K., Arakawa, T., Uchida, T., et al. (1997). In situ expression of cell adhesion molecules in chronic gastritis with Helicobacter pylori infection, J. Clin. Gastroenterol. 25 (Suppl. 1), S215–S221.
Lauritsen, K., Andersen, B. N., Laursen, L. S., et al. (1991). Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse, Gastroenterology 100, 663–669.
Lindley, I., Aschauer, H., Siefert, J.-M., et al. (1988). Synthesis and expression in Escherichia coli of the gene encoding monocyte-derived neutrophil-activating factor: biological equivalence between natural and recombinant neutrophil-activating factor, Proc. Natl. Acad. Sci. USA 85, 9199–9203.
Mai, U.E., Perez-Perez, G. I., Wahl, L. M., et al. (1991). Soluble surface proteins from Helicobacter pylori activate monocytes/ macrophages by lipopolysaccharide-independent mechanism, J. Clin. Invest. 87, 894–900.
Marlim, S. D. and Springer, T. A. (1987). Purified intercellular adhesion molecules-1 (ICAM-1) is a ligand for lymphocyte function-associatedantigen 1 (LFA-1). Cell 51, 813–819.
Marshall, B. J., Goodwin, C. S., Warren, J. R., et al. (1988). Prospective double-blindtrial of duodenal ulcer recurrence after eradication of Campylobacter pylori, Lancet ii, 1437–1442.
Matsushima, K., Morishita, K., Yoshimura, T., et al. (1988). Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor, J. Exp. Med. 167, 1883–1893.
Noach, L. A., Bosma, N. B., Jansen, J., et al. (1994). Mucosal tumor necrosis factor-α, interleukin-1β, and interleukin-8 production in patients with Helicobacter pylori infection, Scand. J. Gastroen-terol. 29, 425–429.
Philip, R. and Epstein, L. B. (1986). Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, γ-interferon and interleukin-1, Nature 323, 86–89.
Pober, J. S., Bevilacqua, M. P., Mendrick, D. L., et al. (1986). Monokines, interleukin-1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells, J. Immunol. 136, 1680–1687.
Pohlman, T. H., Stanness, K. A., Beatty, P. G., et al. (1986). An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin-1, and tumor necrosis factor-α increases neutrophil adherence by a CDw18-dependent mechanism, J. Immunol. 136, 4548–4553.
Santucci, L., Fiorucci, S., Di Matteo, F. M., et al. (1995). Role of tumor necrosis factor α release and leukocyte margination in indomethacin-induced gastric injury in rats, Gastroenterology 108 393–401.
Sica, A., Matsushima, K., van Damme, J., et al. (1990). IL-1 transcriptionallyactivates the neutrophil chemotactic factor/ IL-8 gene in endothelial cells, Immunology 69 548–553.
Springer, T. A. (1990). Adhesion receptors of the immune system, Nature 346, 425–434.
Strieter, R. M., Chensue, S. W., Basha, M. A., et al. (1990). Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-α, lipopolysaccharide, and interleukin-1β, Am. J. Respir. Cell. Mol. Biol. 2, 321–326.
Taha, A. S., Dahill, S., Sturrock, R. D., Lee, F. D., et al. (1994). Predicting NSAID related ulcers-assessment of clinical and pathological risk factors and importance of differences in NSAID, Gut 35, 891–895.
Takagi, K., Okabe, S. and Saziki, R. (1969). A new method for the production of chronic gastric ulcer in rats and the effect of several drugs on its healing, Jpn. J. Pharmacol. 19, 418–426.
Takaishi, O., Arakawa, T., Fujiwara, Y., et al. (1999). Inhibition by 16,16-dimethyl prostaglandin E2 of tumor necrosis factor-alpha and interleukin-1beta production and messenger RNA expression in human monocytes stimulated by Helicobacter pylori, Dig. Dis. Sci. 44, 2405–0411.
Tominaga, K., Arakawa, T., Kim, S., et al. (1997). Increasedexpression of transforminggrowth factor-β1 during gastric ulcer healing in rats, Dig. Dis. Sci. 42, 616–625.
Tominaga, K., Arakawa, T., Watanabe, T., et al. (1998). Increased mRNA levels of transform-ing growth factor-beta1 and monocyte chemoattractant protein-1 in ulcer relapse caused by interleukin-1betain rats, Dig. Dis. Sci. 43 (Suppl. 9), 134S–138S.
Uchida, M., Kawano, O., Misaki, N., et al. (1990). Healing of acetic acid-induced gastric ulcer and gastric mucosal PGI2 level in rats, Dig. Dis. Sci. 35, 80–85.
Wallace, J. L., Keenan, C. M. and Granger, D. N. (1990). Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process, Am. J. Physiol. 259, G462–G467.
Wallace, J. L., Arfors, K.-E. and McKnight, G. W. (1991). A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit, Gastroenterology 100, 878–883.
Wallace, J. L., McKnight, W., Miyasaka, M., et al. (1993). Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury, Am. J. Physiol. 265, G993–G998.
Watanabe, T., Arakawa, T., Fukuda, T., et al. (1995). Zinc deficiency delays gastric ulcer healing in rats, Dig. Dis. Sci. 40, 1340–1344.
Watanabe, T., Arakawa, T., Fukuda, T., et al. (1997). Role of neutrophils in a rat model of gastric ulcer recurrence caused by IL-1β, Am. J. Pathol. 150, 971–979.
Watanabe, T., Arakawa, T., Tominaga, K., et al. (2000). Neutrophil accumulation in development gastric ulcer induced by submucosal injection of endothelin-1 in rats, Dig. Dis. Sci. 45, 880–888.
Watanabe, T., Higuchi, K., Tominaga, K., et al. (2001). Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1beta, Gut 48, 774–781.
Watanabe, T., Higuchi, K., Hamaguchi, M., et al. (2002). Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils, Dig. Dis. Sci. 47, 1582–1589.
Yoshida, N., Granger, D. N., Evans, D. J. Jr., et al. (1993). Mechanisms involved in Helicobacter pylori-induced inflammation, Gastroenterology 105, 1431–1440.
Yoshida, N., Yoshikawa, T., Nakamura, Y., et al. (1995). Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury, Dig. Dis. Sci. 40, 2300–2304.
Rights and permissions
About this article
Cite this article
Watanabe, T., Higuchi, K., Tanigawa, T. et al. Mechanisms of peptic ulcer recurrence: role of inflammation. Inflammopharmacology 10, 291–302 (2002). https://doi.org/10.1163/156856002321544765
Issue Date:
DOI: https://doi.org/10.1163/156856002321544765