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Infection and Immunity, February 2000, p. 664-671, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Cytokine Expression and Production by Purified Helicobacter pylori Urease in Human Gastric Epithelial Cells

Toshihito Tanahashi,1,* Masakazu Kita,2 Tadashi Kodama,1 Yoshio Yamaoka,1 Naoki Sawai,1 Tomoyuki Ohno,1 Shoji Mitsufuji,1 Ya-Ping Wei,2 Kei Kashima,1 and Jiro Imanishi2

Third Department of Internal Medicine,1 and Department of Microbiology,2 Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

Received 14 April 1999/Returned for modification 16 June 1999/Accepted 11 November 1999

Cytokines have been proposed to play an important role in Helicobacter pylori-associated gastroduodenal diseases, but the exact mechanism of the cytokine induction remains unclear. H. pylori urease, a major component of the soluble proteins extracted from bacterial cells, is considered to be one of the virulence factors for the inflammation in the gastric mucosa that is produced in H. pylori infection. However, the response of human gastric epithelial cells to the stimulation of urease has not been investigated. In the present study, we used human gastric epithelial cells in a primary culture system and examined whether H. pylori urease stimulates the gastric epithelial cells to induce proinflammatory cytokines by reverse transcription-PCR and enzyme-linked immunosorbent assay. First, by using peripheral blood mononuclear cells (PBMC) and a gastric cancer cell line (MKN-45 cells), we confirmed the ability of purified H. pylori urease to induce the production of proinflammatory cytokines. Furthermore, we demonstrated that the human gastric epithelial cells produced interleukin-6 (IL-6) and tumor necrosis factor alpha, but not IL-8, following stimulation with purified urease. The patterns of cytokine induction differed among human PBMC, MKN-45 cells, and human gastric epithelial cells. These results suggest that the human gastric epithelial cells contribute to the induction of proinflammatory cytokines by the stimulation of H. pylori urease, indicating that the epithelial cells were involved in the mucosal inflammation that accompanied H. pylori infection.

* Corresponding author. Mailing address: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji Kamigyo-ku, Kyoto 602-8566, Japan. Phone: 81-75-251-5519. Fax: 81-75-251-0710. E-mail: ttana{at}sun.kpu-m.ac.jp.

Infection and Immunity, February 2000, p. 664-671, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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