Skip to main content
Gut logoLink to Gut
. 1998 May;42(5):609–617. doi: 10.1136/gut.42.5.609

Chemokines in the gastric mucosa in Helicobacter pylori infection

Y Yamaoka 1, M Kita 1, T Kodama 1, N Sawai 1, T Tanahashi 1, K Kashima 1, J Imanishi 1
PMCID: PMC1727111  PMID: 9659152

Abstract

Background—Although chemokines have been suggested to play an important role in Helicobacter pylori associated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa. 
Aims—To investigate the expression and production patterns of various chemokines using gastric biopsy specimens. 
Methods—In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated α (GROα)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). cagA gene was identified using PCR. 
ResultsH pylori infection was associated with increased rates of expression of mRNA for IL-8, GROα, RANTES, and MIP-1α and with increased levels of mucosal IL-8 and GROα. IL-8 and GROα levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pylori infection was associated with increased rates of expression of mRNA for IL-8 and GROα and with increased levels of these chemokines. 
ConclusionH pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GROα), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach. 



Keywords: Helicobacter pylori; chemokines; interleukin 8; GROα

Full Text

The Full Text of this article is available as a PDF (195.4 KB).

Figure 1 .

Figure 1

H pylori infection and production of GROα. Bars indicate median values for each group.

Figure 2 .

Figure 2

Relation between mucosal levels of IL-8 and GROα protein in H pylori positive patients.

Figure 3 .

Figure 3

Production of C-X-C chemokines and histological findings in H pylori positive patients with chronic gastritis are expressed as box plots. The ends of the bars indicate the 25th and 75th percentiles. The 50th percentile is indicated with a line, and the 10th and 90th percentiles are indicated with error bars. Data outside the 10th and 90th percentile are displayed using symbols. Correlation coefficients were calculated with the Spearman rank test.

Figure 4 .

Figure 4

Production of GROα and eradication of H pylori. *p<0.005 by Wilcoxon's matched pairs test. Before, before eradication therapy; after, after eradication therapy.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baggiolini M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
  2. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bayerdörffer E., Lehn N., Hatz R., Mannes G. A., Oertel H., Sauerbruch T., Stolte M. Difference in expression of Helicobacter pylori gastritis in antrum and body. Gastroenterology. 1992 May;102(5):1575–1582. doi: 10.1016/0016-5085(92)91716-h. [DOI] [PubMed] [Google Scholar]
  4. Blaser M. J. Epidemiology and pathophysiology of Campylobacter pylori infections. Rev Infect Dis. 1990 Jan-Feb;12 (Suppl 1):S99–106. doi: 10.1093/clinids/12.supplement_1.s99. [DOI] [PubMed] [Google Scholar]
  5. Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14648–14653. doi: 10.1073/pnas.93.25.14648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Crabtree J. E., Peichl P., Wyatt J. I., Stachl U., Lindley I. J. Gastric interleukin-8 and IgA IL-8 autoantibodies in Helicobacter pylori infection. Scand J Immunol. 1993 Jan;37(1):65–70. doi: 10.1111/j.1365-3083.1993.tb01666.x. [DOI] [PubMed] [Google Scholar]
  8. Crabtree J. E., Shallcross T. M., Heatley R. V., Wyatt J. I. Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis. Gut. 1991 Dec;32(12):1473–1477. doi: 10.1136/gut.32.12.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crabtree J. E., Xiang Z., Lindley I. J., Tompkins D. S., Rappuoli R., Covacci A. Induction of interleukin-8 secretion from gastric epithelial cells by a cagA negative isogenic mutant of Helicobacter pylori. J Clin Pathol. 1995 Oct;48(10):967–969. doi: 10.1136/jcp.48.10.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dixon M. F., Genta R. M., Yardley J. H., Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996 Oct;20(10):1161–1181. doi: 10.1097/00000478-199610000-00001. [DOI] [PubMed] [Google Scholar]
  11. Fan X. G., Chua A., Fan X. J., Keeling P. W. Increased gastric production of interleukin-8 and tumour necrosis factor in patients with Helicobacter pylori infection. J Clin Pathol. 1995 Feb;48(2):133–136. doi: 10.1136/jcp.48.2.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gionchetti P., Vaira D., Campieri M., Holton J., Menegatti M., Belluzzi A., Bertinelli E., Ferretti M., Brignola C., Miglioli M. Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients. Am J Gastroenterol. 1994 Jun;89(6):883–887. [PubMed] [Google Scholar]
  13. Hosaka S., Akahoshi T., Wada C., Kondo H. Expression of the chemokine superfamily in rheumatoid arthritis. Clin Exp Immunol. 1994 Sep;97(3):451–457. doi: 10.1111/j.1365-2249.1994.tb06109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoshina S., Kahn S. M., Jiang W., Green P. H., Neu H. C., Chin N., Morotomi M., LoGerfo P., Weinstein I. B. Direct detection and amplification of Helicobacter pylori ribosomal 16S gene segments from gastric endoscopic biopsies. Diagn Microbiol Infect Dis. 1990 Nov-Dec;13(6):473–479. doi: 10.1016/0732-8893(90)90079-b. [DOI] [PubMed] [Google Scholar]
  15. Kameyoshi Y., Dörschner A., Mallet A. I., Christophers E., Schröder J. M. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587–592. doi: 10.1084/jem.176.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kita M., Hayashi T., Yamagishi H., Oka T., Imanishi J. Expression de l'ARN messager des cytokines dans la rate humaine. C R Seances Soc Biol Fil. 1994;188(3):277–282. [PubMed] [Google Scholar]
  17. Lee J., Horuk R., Rice G. C., Bennett G. L., Camerato T., Wood W. I. Characterization of two high affinity human interleukin-8 receptors. J Biol Chem. 1992 Aug 15;267(23):16283–16287. [PubMed] [Google Scholar]
  18. Matsushima K., Oppenheim J. J. Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine. 1989 Nov;1(1):2–13. doi: 10.1016/1043-4666(89)91043-0. [DOI] [PubMed] [Google Scholar]
  19. Moss S. F., Legon S., Davies J., Calam J. Cytokine gene expression in Helicobacter pylori associated antral gastritis. Gut. 1994 Nov;35(11):1567–1570. doi: 10.1136/gut.35.11.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Noach L. A., Bosma N. B., Jansen J., Hoek F. J., van Deventer S. J., Tytgat G. N. Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol. 1994 May;29(5):425–429. doi: 10.3109/00365529409096833. [DOI] [PubMed] [Google Scholar]
  21. Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
  22. Parsonnet J., Friedman G. D., Vandersteen D. P., Chang Y., Vogelman J. H., Orentreich N., Sibley R. K. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. doi: 10.1056/NEJM199110173251603. [DOI] [PubMed] [Google Scholar]
  23. Peek R. M., Jr, Miller G. G., Tham K. T., Perez-Perez G. I., Zhao X., Atherton J. C., Blaser M. J. Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest. 1995 Dec;73(6):760–770. [PubMed] [Google Scholar]
  24. Peterson W. L. Helicobacter pylori and peptic ulcer disease. N Engl J Med. 1991 Apr 11;324(15):1043–1048. doi: 10.1056/NEJM199104113241507. [DOI] [PubMed] [Google Scholar]
  25. Rauws E. A., Langenberg W., Houthoff H. J., Zanen H. C., Tytgat G. N. Campylobacter pyloridis-associated chronic active antral gastritis. A prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterology. 1988 Jan;94(1):33–40. [PubMed] [Google Scholar]
  26. Rot A., Krieger M., Brunner T., Bischoff S. C., Schall T. J., Dahinden C. A. RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. J Exp Med. 1992 Dec 1;176(6):1489–1495. doi: 10.1084/jem.176.6.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schall T. J., Bacon K., Toy K. J., Goeddel D. V. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature. 1990 Oct 18;347(6294):669–671. doi: 10.1038/347669a0. [DOI] [PubMed] [Google Scholar]
  28. Schall T. J. Biology of the RANTES/SIS cytokine family. Cytokine. 1991 May;3(3):165–183. doi: 10.1016/1043-4666(91)90013-4. [DOI] [PubMed] [Google Scholar]
  29. Sharma S. A., Tummuru M. K., Miller G. G., Blaser M. J. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun. 1995 May;63(5):1681–1687. doi: 10.1128/iai.63.5.1681-1687.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stolte M., Eidt S., Ohnsmann A. Differences in Helicobacter pylori associated gastritis in the antrum and body of the stomach. Z Gastroenterol. 1990 May;28(5):229–233. [PubMed] [Google Scholar]
  31. Taub D. D., Oppenheim J. J. Chemokines, inflammation and the immune system. Ther Immunol. 1994 Aug;1(4):229–246. [PubMed] [Google Scholar]
  32. Tummuru M. K., Cover T. L., Blaser M. J. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993 May;61(5):1799–1809. doi: 10.1128/iai.61.5.1799-1809.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tummuru M. K., Sharma S. A., Blaser M. J. 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 Dec;18(5):867–876. doi: 10.1111/j.1365-2958.1995.18050867.x. [DOI] [PubMed] [Google Scholar]
  34. Yamaoka Y., Kita M., Kodama T., Sawai N., Imanishi J. Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. Gastroenterology. 1996 Jun;110(6):1744–1752. doi: 10.1053/gast.1996.v110.pm8964399. [DOI] [PubMed] [Google Scholar]
  35. Yamaoka Y., Kita M., Kodama T., Sawai N., Kashima K., Imanishi J. Expression of cytokine mRNA in gastric mucosa with Helicobacter pylori infection. Scand J Gastroenterol. 1995 Dec;30(12):1153–1159. doi: 10.3109/00365529509101624. [DOI] [PubMed] [Google Scholar]
  36. Yamaoka Y., Kita M., Kodama T., Sawai N., Kashima K., Imanishi J. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains. Gut. 1997 Oct;41(4):442–451. doi: 10.1136/gut.41.4.442. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES