STOMACH

Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells

S Futagami, T Hiratsuka, A Tatsuguchi, K Suzuki, M Kusunoki, Y Shinji, K Shinoki, T Iizumi, T Akamatsu, H Nishigaki, K Wada, K Miyake, K Gudis, T Tsukui and C Sakamoto

Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

Correspondence to:
Correspondence to:
Dr C Sakamoto, Third Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan;
choitsu{at}nms.ac.jp

Background and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation.

Methods: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C–C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon (IFN-), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry.

Results: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN- but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN- secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related.

Conclusions: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.

Keywords: Helicobacter pylori; T cell; cyclooxygenase; COX-2 inhibitor; mucosal immunity

Abbreviations: MCP-1, monocyte chemoattractant protein 1; COX, cyclooxygenase; IL, interleukin; IFN- interferon ; PG, prostaglandin; HPWEP, Helicobacter pylori water extract protein; FCS, fetal calf serum; NFB, nuclear factor B; MIP, macrophage inflammatory protein; ELISA, enzyme linked immunosorbent assay; RT-PCR, reverse transcription-polymerase chain reaction; TBS, Tris buffered saline; LPS, lipopolysaccharide; Th, T helper

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