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5‐LOX Inhibitor Modulates the Inflammatory Responses Provoked by Helicobacter pylori Infection
Author(s) -
Park Soojin,
Han SangUk,
Lee KeeMyung,
Park Kyung Ha,
Cho Sung Won,
Hahm KiBaik
Publication year - 2007
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/j.1523-5378.2007.00469.x
Subject(s) - arachidonate 5 lipoxygenase , nordihydroguaiaretic acid , helicobacter pylori , proinflammatory cytokine , arachidonic acid , lipoxygenase , inflammation , tumor necrosis factor alpha , biology , pharmacology , chemistry , immunology , biochemistry , enzyme , genetics
Background: Arachidonic acid metabolites have been considered as pivotal mediators in Helicobacter pylori ‐induced inflammatory response, which are mainly metabolized by two distinct enzymes: cyclooxygenase (COX) and lipoxygenase (LOX). While COX has become well known to play a key role in either carcinogenesis or inflammation related to H. pylori infection, little is known regarding the implication of LOX in H. pylori infection. In this study, we evaluated the roles of 5‐LOX and its metabolites in H. pylori ‐induced host responses and further a potential beneficial action of specific LOX inhibitors against H. pylori infection. Materials and Methods: Expressions of cytosolic phospholipase A 2 (cPLA 2 ), COX‐2, and 5‐LOX after H. pylori infection were evaluated by immunofluorescence staining and Western blotting. Synthesis of LOX metabolites was measured with reversed‐phase high‐performance liquid chromatography. For analyzing the influence of 5‐LOX inhibitors, nordihydroguaiaretic acid (NDGA) and geraniin, on H. pylori ‐induced inflammatory responses, RNase protection assay and RT‐PCR were performed. Results: H. pylori stimulated the translocation of cPLA 2 from cytoplasm to nucleus and increased the biosynthesis of hydroxyeicosatetraenoic acids (HETEs) as a predominant form of 5S‐HETE in gastric epithelium. NDGA exerted a strong suppression activity of H. pylori ‐induced 5‐LOX signaling. The administration of LOX inhibitors was related with down‐expression of proinflammatory mediators such as interleukin‐8 and tumor necrosis factor‐α in both H. pylori ‐infected gastric epithelial cells and macrophage cells. Conclusion: LOX modulation with its specific inhibitors could impose significant anti‐inflammatory responses after H. pylori infection, based on the fact that H. pylori infection provoked gastric inflammation through metabolizing arachidonic acid by the 5‐LOX pathway.