J Bacteriol Virol.  2008 Dec;38(4):227-234. 10.4167/jbv.2008.38.4.227.

Expression of CCL18 (Dendritic Cell-Derived Chemokine) mRNA in Gastric Mucosa Infected with Helicobacter pylori

• Park HY
• Jo EK
• Kim HJ
• Park JK

• KMID: 1483963
• DOI: http://doi.org/10.4167/jbv.2008.38.4.227

Abstract

Helicobacter pylori (H. pylori) is a major etiologic agent causing chronic gastritis, along with other features, including lymphoid follicles, surface epithelial degeneration with mucous depletion and intestinal metaplasia. To clarify the mechanism by which H. pylori induces gastric mucosal injury and development of lymphoid follicles, in this study we examined the expression of the iNOS, cagA, CCL3 and CCL18 mRNA in biopsy materials obtained from severe and mild chronic gastritis. Reverse transcription-PCR analysis showed that the rate of iNOS expression in mucosa of severe or mild chronic gastritis was 95.7% or 92.9, respectively. The expression of cagA mRNA in mucosa of severe chronic gastritis was 63.8%, but cagA mRNA was not found in mucosa of mild chronic gastritis. The expression of CCL3 mRNA in mucosa of severe chronic gastritis was 95.7%, but CCL3 mRNA was not found in mucosa of mild chronic gastritis. The expression of CCL18 mRNA was 53.2% in lymphoid follicle of gastric mucosa, but CCL18 mRNA was found in gastric mucosa without lymphoid follicle (46.8%). The prevalence of expression of both cagA and CCL18 mRNA was 59.6% and cagA mRNA expression without CCL18 was 16.7% in lymphoid follicle of gastric mucosa. These results suggest that the expression of iNOS mRNA in both mild and severe chronic gastritis is very high, therefore, the NO pathway is suspected of being an important factor in the etiology of chronic gastritis. The expression of cagA mRNA in gastric mucosa is associated with severity of chronic gastritis. Almost all of the CCL18 mRNA positive gastric mucosa were also expressing cagA, therefore CCL18 mRNA expression is closely related to the cagA mRNA expression (p<0.0001).

Keyword

Helicobacter pylori; Lymphoid follicle; cagA; CCL18

MeSH Terms

Biopsy
Gastric Mucosa
Gastritis
Helicobacter
Helicobacter pylori
Metaplasia
Mucous Membrane
Prevalence
RNA, Messenger
RNA, Messenger

Reference

1). Adema GJ., Hartgers F., Verstraten R., de Vries E., Marland G., Menon S., Foster J., Xu Y., Nooyen P., McClanahan T., Bacon KB., Figdor CG. A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells. Nature. 387:713–717. 1997.

2). Bayerdrffer E., Lehn N., Hatz R., Mannes GA., Oertel H., Sauerbruch T., Stolte M. Difference in expression of Helicobacter pylori gastritis in antrum and body. Gastroenterology. 102:1575–1582. 1992.

3). Choi IJ., Kim JS., Jung HC., Kim JM., Lee KL., Son IS., Kim CY. Expression of CXC and CC chemokines in the gastric mucosa infected with Helicobacter pylori. Korean J Gastroenterol. 36:163–174. 2000.

4). Correa P. Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol. 83:504–509. 1988.

5). Crabtree JE. Role of cytokines in pathogenesis of Helocobacter pylori-induced mucosal damage. Dig Dis Sci. 43:46S–55S. 1998.

6). Crabtree JE., Farmery SM., Lindley IJ., Figura N., Peichl P., Tompkins DS. CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J Clin Pathol. 47:945–950. 1994.

7). Crawford JM. The gastrointestinal tract. pp. p. 797–875. In. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Kumar V, Abbas AK, Fausto N, editors. (Ed),. Elsevier Saunders;Philadelphia: 2005.

8). Dixon MF., Genta RM., Yardley JH., Correa P. Classification and grading of gastiritis: the update Sydney system. International Workshop of Gastritis, Houston, 1994. Am J Surg Pathol. 20:1161–1181. 1996.

9). Drake IM., Mapstone NP., Schorah CJ., White KL., Chalmers DM., Dixon MF., Axon AT. Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori-associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H. pylori eradication. Gut. 42:768–771. 1998.

10). Hansen PS., Go MF., Varming K., Andersen LP., Genta RM., Graham DY., Nielsen H. Proinflammatory activation of neutrophils and monocytes by Helicobacter pylori in patients with different clinical presentations. Infect Immun. 67:3171–3174. 1999.

11). Hatz RA., Rieder G., Stolte M., Bayerdrffer E., Meimarakis G., Schildberg FW., Enders G. Pattern of adhesion molecule expression on vascular endothelium in Helicobacter pylori-associated antral gastritis. Gastroenterology. 112:1908–1919. 1997.

12). Hofman VJ., Moreilhon C., Brest PD., Lassalle S., Brigand KL., Sicard D., Raymond J., Lamarwue D., Hbuterne XA., Mari B., Barbry PJP., Hofman PM. Gene expression profiling in human gastric mucosa infected with Helicobacter pylori. Modern Pathol. 20:974–989. 2007.

13). Husson MO., Gottrand F., Vachee A., Dhaenens L., de la Salle EM., Turck D., Houcke M., Leclerc H. Importance in diagnosis of gastritis of detection by PCR of the cagA gene in Helicobacter pylori strains isolated from children. J Clin Microbiol. 33:3300–3303. 1995.

14). Jung HC., Kim JM., Song IS., Kim CY. Helicobacter pylori induced an array of pro-inflammatory cytokines in human gastric epithelial cells: quantification of mRNA for interleukin-8, −1 alpha/beta, granulocyte-macrophage colony-stimulting factor, monocyte chemoattractant protein-1 and tumor necrosis factor-alpha. J Gastroenterol Hepatol. 12:473–480. 1997.

15). Kim DY. The positive rates of Helicobacter pylori cagA gene in gastric biopsy specimens of the patients with gastritis, gastric ulcer, duodenal ulcer, and gastric cancer and comparison of the degree of the gastritis. Korean J Gastroenterol. 32:24–31. 1998.

16). Kim SW., Chung IS., Lee KM., Lee DS., Yoon JG., Kim SS., Yang YS., Choi MG., Han SW., Choi KY., Park DH. Comparison of intestinal metaplasia and serum pepsinogen levels between Helicobacter pylori-infected duodenal ulcer and chronic gastritis. Korean J Gastroenterol. 36:155–162. 2000.

17). Korean Helicobacter pylori study group. Diagnosis and treatment of Helicobacter pylori infection in Korea. Korean J Gastroenterol. 32:275–289. 1998.

18). Kusano F., Tanaka Y., Marumo F., Sato C. Expression of C-C chemokines is associated with portal and periportal inflammation in the liver of patients with chronic hepatitis C. Lab Invest. 80:415–422. 2000.

19). Li CQ., Pignatelli B., Ohshima H. Coexpression of interleukin-8 and inducible nitric oxide synthase in gastric mucosa infected with cagA Helicobacter pylori. Dig Dis Sci. 45:55–62. 2000.

20). Marshall BJ., Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1:1311–1315. 1984.

21). Peek RM Jr., Miller GG., Tham KT., Prez-Prez GI., Cover TL., Atherton JC., Dewey Dunn G., Blaser MJ. Detection of Helicobacter pylori gene expression in human gastric mucosa. J Clin Microbiol. 33:28–32. 1995.

22). Price AB. The Sydney system: histological division. J Gastroenterol Hepatol. 6:209–222. 1991.

23). Sato Y., Sugimura K., Mochizuki T., Honma T., Suriki H., Tashiro K., Ishizuka K., Narisawa R., Ichida T., Van Thiel DH., Asakura H. Regionl differences on production of chemokines in gastric mucosa between Helicobacter pylori-positive duodenal ulcer and gastric ulcer. Dig Dis Sci. 44:2390–2396. 1999.

24). Shimoyama T., Everett SM., Dixon MF., Axon AT., Crabtree JE. Chemokine mRNA expression in gastric mucosa is associated with Helicobacter pylori cagA positivity and severity of gastritis. J Clin Pathol. 51:765–770. 1998.

25). Tatemichi M., Ogura T., Nagata H., Esumi H. Enhanced expression of inducible nitric oxide synthase in chronic gastritis with intestinal metaplasia. J Clin Gastroenterol. 27:240–245. 1998.

26). Tursi A., Gasbarrini G. Acquired gastric mucosa-associated lymphoid tissue (MALT): a review with special emphasis on association with extragastric diseases and management problems of gastric MALT. J Clin Gastroenterol. 29:133–137. 1999.

27). Yamaoka Y., Kita M., Kodama T., Sawai N., Imanishi J. Helicobcter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. Gastroenterology. 110:1744–1752. 1996.

28). 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 Helicobcter pylori strains. Gut. 41:442–451. 1997.

29). Yamaoka Y., Kita M., Kodama T., Sawai N., Tanahashi T., Kashima K., Imanishi J. Chemokines in the gastric mucosa in Helicobcter pylori infection. Gut. 42:609–617. 1998.

30). Yang US., Cho M., Kang DH., Song CS., Song GA., Park SK. The prevalence of cagA+Helicobcter pylori in the peptic ulcer diseases. Korean J Gastroenterol. 31:184–191. 1998.

31). Zaitoun AM. The prevalence of lymphoid follicles in Helicobacter pylori associated gastritis in patients with ulcers and non-ulcer dyspepsia. J Clin Pathol. 48:325–329. 1995.

32). Zlotnik A., Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 12:121–127. 2000.