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5-LOX inhibitor modulates the inflammatory responses provoked by Helicobacter pylori infection.

Abstract

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-alpha 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.

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  • Authors+Show Affiliations

    ,

    Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Bundang Jesaeng Hospital, Seongnam, Korea.

    , , , ,

    Source

    Helicobacter 12:1 2007 Feb pg 49-58

    MeSH

    Animals
    Arachidonate 5-Lipoxygenase
    Arachidonic Acid
    Cell Line
    Down-Regulation
    Epithelial Cells
    Glucosides
    Helicobacter Infections
    Helicobacter pylori
    Humans
    Hydrolyzable Tannins
    Interleukin-8
    Lipoxygenase Inhibitors
    Macrophages
    Masoprocol
    Mitogen-Activated Protein Kinase 3
    NF-kappa B
    Oxidation-Reduction
    Signal Transduction
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17241301

    Citation

    Park, Soojin, et al. "5-LOX Inhibitor Modulates the Inflammatory Responses Provoked By Helicobacter Pylori Infection." Helicobacter, vol. 12, no. 1, 2007, pp. 49-58.
    Park S, Han SU, Lee KM, et al. 5-LOX inhibitor modulates the inflammatory responses provoked by Helicobacter pylori infection. Helicobacter. 2007;12(1):49-58.
    Park, S., Han, S. U., Lee, K. M., Park, K. H., Cho, S. W., & Hahm, K. B. (2007). 5-LOX inhibitor modulates the inflammatory responses provoked by Helicobacter pylori infection. Helicobacter, 12(1), pp. 49-58.
    Park S, et al. 5-LOX Inhibitor Modulates the Inflammatory Responses Provoked By Helicobacter Pylori Infection. Helicobacter. 2007;12(1):49-58. PubMed PMID: 17241301.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 5-LOX inhibitor modulates the inflammatory responses provoked by Helicobacter pylori infection. AU - Park,Soojin, AU - Han,Sang-Uk, AU - Lee,Kee-Myung, AU - Park,Kyung Ha, AU - Cho,Sung Won, AU - Hahm,Ki-Baik, PY - 2007/1/24/pubmed PY - 2007/3/16/medline PY - 2007/1/24/entrez SP - 49 EP - 58 JF - Helicobacter JO - Helicobacter VL - 12 IS - 1 N2 - 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-alpha 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. SN - 1083-4389 UR - https://www.unboundmedicine.com/medline/citation/17241301/5_LOX_inhibitor_modulates_the_inflammatory_responses_provoked_by_Helicobacter_pylori_infection_ L2 - https://doi.org/10.1111/j.1523-5378.2007.00469.x DB - PRIME DP - Unbound Medicine ER -