title: Increased expression and cellular localization of lipocalin-type prostaglandin D synthase in Helicobacter pylori-induced gastritis.
abstract: Immunological responses in the host can result in different disease outcomes of Helicobacter pylori-induced gastritis. Prostaglandin E2 derived from cyclooxygenase (COX) and prostaglandin E synthase contribute to gastric protection. Recently, prostaglandin D2 was shown to be involved in host immunity by chemotactic activity through chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), but its role in H. pylori-induced gastritis has not been clarified. We determined the expression levels of mRNAs for haematopoietic PGD synthase (H-PGDS) and lipocalin-type PGDS (L-PGDS), MIP-1 alpha, IFN-gamma, IL-4, and CDX2 in H. pylori-induced gastritis mucosa by quantitative RT-PCR. We found that L-PGDS was constitutively expressed in the epithelium of the glandular base. L-PGDS, but not H-PGDS, was induced on fibroblasts close to infiltrating cells in the H. pylori-infected gastric mucosa. These fibroblasts co-expressed COX-2. The level of L-PGDS mRNA expression decreased as gastritis became more severe. In most of the H. pylori-infected gastric mucosa, CCR5(+) cells had more actively infiltrated than had CRTH2(+) cells. However, the expression level of IFN-gamma was lower in the mucosa of the CRTH2(+) cells-dominantly infiltrating group than that of the less CRTH2-infiltrating group. Exogenously added PGD2 decreased the H. pylori-induced expression of IFN-gamma in peripheral blood mononuclear cells in vitro. The data suggest that PGD2 derived from the gastric mucosa and fibroblasts plays protective roles against inflammatory changes in H. pylori-induced gastritis.
authors.affiliation: Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan. ryota@ndmc.ac.jp
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
authors.forename: Nanae
authors.initials: N
authors.lastname: Nagata
authors.forename: Chie
authors.initials: C
authors.lastname: Kurihara
authors.forename: Chikako
authors.initials: C
authors.lastname: Watanabe
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Komoto
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Okada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nagao
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.forename: Kinya
authors.initials: K
authors.lastname: Nagata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071616:CDX2 Transcription Factor; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000276:immunology; D005756:Gastritis / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects; D016481:Helicobacter Infections / Q000150:complications* / Q000201:enzymology / Q000276:immunology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D054405:Chemokine CCL3; D016207:Cytokines; D018398:Homeodomain Proteins; D054834:Lipocalins; D019713:Receptors, CCR5; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D007371:Interferon-gamma; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor