Molecular inflammation

Current Opinion in Gastroenterology

Volumn 17, Issue SUPPL. 1, 2001, Pages

  Elliott, Susan N ^a   Ernst, Peter B ^a,b   Kelly, Ciarán P ^c  

^a University of Texas Medical Branch School of Medicine   (United States)

^b UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0010046030     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (46)

1. Fan XJ, Crowe SE, Behar S, et al. The effect of class II MHC expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: a mechanism for Th1 cell-mediated damage. J Exp Med 1998; 187:1659-1669.
2. Fan X, Gunasena H, Cheng Z, et al. Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis. J Immunol 2000; 165:1918-1924. This paper describes the binding of urease to class II MHC, and provides evidence for receptor-mediated signaling to the epithelial cell. The data suggest that urease behaves in an manner analogous to that of other bacterial superantigens.
3. Jenks PJ, Kusters JG. Pathogenesis and virulence factors of Helicobacter pylori. Curr Opin Gastroenterol 2000; 16(suppl):s11-s18.
4. Rautemaa R, Rautelin H, Puolakkainen P, et al. Survival of Helicobacter pylori from complement lysis by binding of GPI- anchored protectin (CD59). Gastroenterology 2001; 120:470-479. H. pylori binding of the lipid-tailed form of the membrane regulator protectin (CD59) protected CagA-positive strains against complement killing, in vitro. Gastric biopsy specimens from H. pylori-infected patients showed that H. pylori bacteria within the gastric pits were often positive for protectin, but negative for C5b-9.
5. Sung JJ, Leung WK, Go MY, et al. Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol 2000; 157:729-735.
6. Tatsuguchi A, Sakamoto C, Wada K, et al. Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans. Gut 2000; 46:782-789.
7. Jackson LM, Wu KC, Mahida YR, et al. Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa. Gut 2000; 47: 762-770.
8. Takahashi S, Fujita T, Yamamoto A. Role of cyclooxygenase-2 in Helicobacter pylori- induced gastritis in Mongolian gerbils. Am J Physiol Gastrointest Liver Physiol 2000; 279:G791-G798. Using H. pylori-infected Mongolian gerbils, cyclo-oxygenase-1 was detected in normal and infected mucosa, whereas cyclo-oxygenase-2 was only observed in H. pylori-infected mucosa. NS-398 and indomethacin inhibited the increased prostaglandin production observed during H. pylori infection, and neither drug had any effect on viable H. pylori levels in the mucosa. Both drugs did potentiate the H. pylori-increased neutrophil chemokine and interferon-γ production.
9. Satin B, Del Giudice G, Della B, et al. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. J Exp Med 2000; 191:1467-1476. This thorough study describes the role of HP-NAP as a trigger of host responses.
10. Kuwahara H, Miyamoto Y, Akaike T, et al. Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production. Infect Immun 2000; 68:4378-4383. This is a description of one mechanism by which H. pylori may evade immunity.
11. Eck M, Schmausser B, Scheller K, et al. CXC chemokines Gro(alpha)/IL-8 and IP-10/MIG in Helicobacter pylori gastritis. Clin Exp Immunol 2000; 122:192-199. In H. pylori gastritis, macrophages within the gastric lamina propria are major sources for the neutrophil attracting CXC chemokines interleukin-8 and Gro-α, as demonstrated by both in-situ hybridization and immunohistochemistry. Chemokine production by lamina propria macrophages and endothelial cells probably plays a critical role in the activation and recruitment of both neutrophils and T cells to the gastric mucosa in H. pylori gastritis.
12. Hofman V, Ricci V, Galmiche A, et al. Effect of Helicobacter pylori on polymorphonuclear leukocyte migration across polarized T84 epithelial cell monolayers: role of vacuolating toxin VacA and cag pathogenicity island. Infect Immun 2000; 68:5225-5233. Strains of H. pylori with an intact cag pathogenicity island are more potent in activating basolateral interleukin-8 secretion and polymorphonuclear leukocyte transmigration across T84 intestinal epithelial cell monolayers. VacA, the H. pylori-vacuolating cytotoxin, does not appear to be necessary to induce these epithelial cell effects.
13. Orsini B, Ciancio G, Censini S, et al. Helicobacter pylori cag pathogenicity-island is associated with enhanced interleukin-8 expression in human gastric mucosa. Dig Liver Dis 2000; 32:458-467. Infection with cag-positive H. pylori is associated with increased interleukin-8 messenger RNA and protein levels, more severe gastritis, and increased bacterial density in studies of human gastric mucosal biopsy specimens.
14. Day AS, Jones NL, Lynett JT, et al. cagE is a virulence factor associated with Helicobacter pylori-induced duodenal ulceration in children. J Infect Dis 2000; 181:1370-1375. This report is of interest because it relates a bacterial gene product to a specific host response in vitro. In addition, these observations are related to a higher incidence of duodenal ulcer in children.
15. Tummuru MKR, Sharma SA, Blaser MJ. Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. Mol Microbiol 1995; 18:867-876.
16. Ogura K, Maeda S, Nakao M, et al Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil. J Exp Med 2000; 192:1601-1610. The importance of an intact cag pathogenicity island in H. pylori virulence was demonstrated in vivo by infecting gerbils with wild-type cag-positive H. pylori or with an isogenic strain carrying a mutation of cagE, a gene that appears to be essential for a functioning bacterial secretion system. In this animal model knocking out CagE substantially reduced the severity of gastritis. These studies further support a role for CagE in the pathogenesis of gastritis.
17. Israel DA, Salama N, Arnold CN, et al. Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses. J Clin Invest 2001; 107:611-620. A cag-positive H. pylori strain induced severe gastritis, apoptosis, atrophy, and gastric ulceration in gerbils. The investigators then used a recently developed H. pylori whole genome microarray to identify differences in gene content between specific H. pylori strains. Naturally occurring or experimentally induced mutations of the H. pylori cag region were associated with decreased gastric mucosal inflammation in vivo, and this correlated with reduced potency in activating interleukin-8 gene expression or apoptosis in vitro. These studies again confirm the importance of an intact cag pathogenicity island in H. pylori virulence and the power of microarray analysis.
18. Peek RM Jr. IV. Helicobacter pylori strain-specific activation of signal transduction cascades related to gastric inflammation. Am J Physiol Gastrointest Liver Physiol 2001; 280:G525-G530.
19. van Den Brink GR, ten Kate FJ, Ponsioen CY, et al. Expression and activation of NF-kappa B in the antrum of the human stomach. J Immunol 2000; 164:3353-3359.
20. Isomoto H, Mizuta Y, Miyazaki M, et al. Implication of NF-kappaB in Helicobacter pylori-associated gastritis. Am J Gastroenterol 2000; 95:2768-2776. The transcription factor NF-κB regulates the expression of a wide variety of proinflammatory cytokines and cellular adhesion molecules. This study confirms that H pylori gastritis is associated with increased NF-κB activation in gastric epithelial cells in vivo, as well as in macrophages, lymphocytes, and vascular endothelial cells. NF-κB activation was correlated with the severity of gastritis, interleukin-8 protein levels, and endothelial cell intercellular adhesion molecule-1 expression.
21. Maeda S, Yoshida H, Ogura K, et al. H. pylori activates NF-kappaB through a signaling pathway involving IkappaB kinases, NF-kappaB-inducing kinase, TRAF2, and TRAF6 in gastric cancer cells. Gastroenterology 2000; 119:97-108. This study examined the signaling events that precede NF-κB activation in gastric epithelial cell lines. H. pylori activated both IκB kinase α and β, leading to phosphorylation and degradation of the inhibitory protein IκBα, thereby releasing activated NF-κB. IκB kinase activation appeared to require NF-κB-inducing kinase activity, as well as the adaptor proteins TNF-receptor-associated factor-2 and -6.
22. Foryst-Ludwig A, Naumann M. p21 -activated kinase 1 activates the nuclear factor kappa B (NF-kappa B)-inducing kinase-Ikappa B kinases NF-kappa B pathway and proinflammatory cytokines in Helicobacter pylon infection. J Biol Chem 2000; 275:39779-39785. H. pylori infection of epithelial cells results in activation of p21-activated kinase 1, which in turn associates with and activates NF-κB-inducing kinase. NF-κB-inducing kinase then activates the IκB kinases, which phosphorylate the inhibitory protein IκBα, leading to its degradation. Activated NF-κB is thereby released to translocate to the nucleus where it can regulate the expression of a wide variety of inflammatory response genes.
23. Keates S, Keates AC, Warny M, et al. Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag-Helicobacter pylori. J Immunol 1999; 163:5552-5559.
24. Naumann M, Wessler S, Bartsch C, et al. Activation of activator protein 1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the cag pathogenicity island. J Biol Chem 1999; 274:31655-31662.
25. Meyer-Ter-Vehn T, Covacci A, et al. Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the protooncogenes c-fos and c-jun. J Biol Chem 2000; 275:16064-16072. This study focuses on activation of the transcription factor AP-1 in gastric epithelial cells. Exposure of a gastric epithelial cell line to H. pylori resulted in ERK MAPK activation and strong induction of AP-1 comprised of c-fos and c-jun. Activation of ERK also resulted in Elk-1 phosphorylation, leading to an increase in c-fos proto-oncogene transcription. These important epithelial cell activation events are dependent on H. pylori cag pathogenicity island gene products.
26. Takahashi S, Keto Y, Fujita T, et al. FR167653, a p38 mitogen-activated protein kinase inhibitor, prevents Helicobacter pylori-induced gastritis in Mongolian gerbils. J Pharmacol Exp Ther 2001; 296:48-56. FR167653, a p38α MAPK inhibitor, reduced both neutrophil infiltration and gastric mucosal injury in H. pylori-infected Mongolian gerbils. These findings illustrate the importance of the p38 MAPK cascade in regulating the host inflammatory response to H. pylori infection.
27. Yamaoka Y, Kwon DH, Graham DY. A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci USA 2000; 97:7533-7538. Sequence analysis of the H. pylori genome indicates 32 putative outer membrane proteins. Mutation of one of these genes (HP0638) substantially reduced H. pylori-induced interleukin-8 protein secretion by gastric epithelial cell lines. The effect of the HP0638 gene product, designated outer inflammatory protein A, on epithelial cell IL-8 production does not appear to depend on the H. pylori cag pathogenicity island. Thus, virulence factors outside the cag region appear to be involved in activating proinflammatory response genes, and may contribute to strain-specific differences in the clinical outcomes of H. pylori infection.
28. Morgner A, Lehn N, Andersen LP, et al. Helicobacter heilmannii-associated primary gastric low-grade MALT lymphoma: complete remission after curing the infection. Gastroenterology 2000; 118:821-828. This study describes the clinical, pathologic, microbiologic, and molecular features of five patients with primary gastric low-grade MALT lymphoma associated with H. heilmannii infection. Treatment resulted in H. heilmannii eradication, and complete endoscopic and histologic tumor remission.
29. Raderer M, Pfeffel F, Pohl G, et al. Regression of colonic low grade B cell lymphoma of the mucosa associated lymphoid tissue type after eradication of Helicobacter pylori. Gut 2000; 46:133-135.
30. Croinin TO, Clyne M, Appelmelk BJ, Drumm B. Antigastric autoantibodies in ferrets naturally infected with Helicobacter mustelae. Infect Immun 2001; 69:2708-2713.
31. +-ATPase, suggesting that T-cell reactivity is not due to an inflammatory milieu per se, but that reactivity arises from specific T-cell epitopes that are shared.
32. Smythies LE, Waites KB, Lindsey JR, et al. Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice. J Immunol 2000; 165:1022-1029. Interleukin-4 knockout mice demonstrated severe gastric inflammation and high levels of interferon-γ in urease-stimulated splenic T cell cultures, whereas interferon-γ-knockout mice were devoid of gastric inflammation and splenic T cell cultures produced predominantly interleukin-4 in response to urease. Upregulation of the Th1-type cytokine interferon-γ, in the absence of modulation by the Th2-type cytokine interleukin-4, is important in promoting H. pylori-associated mucosal inflammation.
33. Sommer F, Faller G, Rollinghoff M, et al. Lack of gastritis and of an adaptive immune response in interferon regulatory factor-1-deficient mice infected with Helicobacter pylori. Eur J Immunol 2001; 31:396-402. A study that examined the functional relevance of a Th1-type response during H. pylori strain SS1 infection in C57BL/6 and interferon regulatory factor-1-deficient mice. Four months after infection, severe gastritis, gastric atrophy, and a Th1-type response were noted in C57BL/6 mice, whereas the lack of a Th1 response in the interferon regulatory factor-1-null mice was associated with a lack of gastritis and atrophy despite colonization with H. pylori.
34. Haeberle H, Kubin M, Bamford KB, et al. Induction of IL-12 and selection of Th1 cells in the gastric mucosa in response to H. pylori. Infect Immun 1997; 65:4229-4235.
35. Tomita T, Jackson AM, Hida N, et al. Expression of interleukin-18, a Th1 cytokine, in human gastric mucosa is increased in Helicobacter pylori infection. J Infect Dis 2001; 183:620-627. This is the first report describing the expression of this cytokine in the gastric mucosa.
36. Ren Z, Pang G, Clancy R, et al. Shift of the gastric T-cell response in gastric carcinoma. J Gastroenterol Hepatol 2001; 16:142-148.
37. Luzza F, Parrello T, Monteleone G, et al. Up-regulalion of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa. J Immunol 2000; 165:5332-5337. This is the first report describing the expression and function of interleukin-17 in interleukin-8 regulation during infection. The approach is very thorough and convincing, and illustrates the complex interactions between the bacteria, T cells, epithelial cells, and neutrophils.
38. Saldinger PF, Porta N, Launois P, et al. Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection. Gastroenterology 1998; 115:891-897.
39. Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy. Nature Med 2000; 6:536-542. A very interesting concept is presented that suggests that T-cell phenotype is important in regulating gastritis. It also provides a model by which people infected with H. pylori and helminths might expect to have a different clinical outcome than infected persons in more developed countries. Limitations of the interpretation of these experiments exist, as discussed by MacDonald [40].
40. MacDonald TT. The worm turns on Helicobacter pylori. Gut 2001; 48: 10-11.
41. Houghton J, Macera-Bloch LS, Harrison L, et al. Tumor necrosis factor alpha and interleukin 1beta up-regulate gastric mucosal Fas antigen expression in Helicobacter pylori infection. Infect Immun 2000;68: 1189-1195. This paper describes the regulation of Fas and cell death in an animal model. These events are probably important in the pathogenesis of epithelial cell damage.
42. Wang J, Fan XJ, Lindholm C, et al. Helicobacter pylori modulates lymphoepithelial cell interactions leading to epithelial cell damage through Fas/FasLigand interactions. Infect Immun 2000; 68:4303-4311. Like the work of Houghton et al. [41*], this work describes the regulation of Fas and cell death, but in humans. The role of gastric T cells in mediating this process is also described.
43. Ramsdell F, Seaman MS, Miller RE, et al. Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death. Int Immunol 1994; 6:1545-1553.
44. Koyama S. Apoptotic depletion of infiltrating mucosal lymphocytes associated with Fas ligand expression by Helicobacter pylori-infected gastric mucosal epithelium: human glandular stomach as a site of immune privilege. Dig Dis Sci 2000; 45:773-780.
45. Michetti M, Kelly CP, Kraehenbuhl JP, et al. Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune protection against helicobacter infection in mice. Gastroenterology 2000; 119:109-118. This study provides new information on the recruitment of immune T cells for conferring immunity after vaccination.
46. Shirai Y, Wakatsuki Y, Kusumoto T, et al. Induction and maintenance of immune effector cells in the gastric tissue of mice orally immunized to Helicobacter pylori requires salivary glands. Gastroenterology 2000; 118:749-759. This paper introduces a very novel concept that protection after vaccination may be regulated or mediated by factors that are very remote from the stomach.