title: PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia.
abstract: Prostaglandin D2 (PGD2) is a major prostanoid secreted mainly by mast cells. Although PGD2 has been identified as a modulator of allergic inflammation, its precise role remains unclear. Here we investigate the role of PGD2 in food allergy. Oral administration of ovalbumin induces allergic responses in sensitized wild-type (WT) mice. Systemic gene deficiency of haematopoietic PGD synthase (H-PGDS(-/-)) exacerbates all of the manifestations accompanying severe mast cell hyperplasia in the intestine. Morphological studies show that c-kit/FcɛRI-positive WT mast cells strongly express H-PGDS. Transplantation of H-PGDS(-/-) mast cells also aggravates ovalbumin-induced mast cell hyperplasia and allergic symptoms in mast cell null mice. H-PGDS deficiency accelerates the production of SDF-1α and the activity of MMP-9 in the antigen-stimulated intestine. SDF-1α receptor blockade or MMP-9 inhibition relieves the exacerbated mast cell hyperplasia and manifestations observed in H-PGDS(-/-). Thus, PGD2 deficiency results in food antigen-induced mast cell hyperplasia.
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Morphological and Physiological Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Horiguchi
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Toko
authors.initials: T
authors.lastname: Maehara
authors.affiliation: International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul 136-701, Korea.
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Choi
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.affiliation: Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D054377:Chemokine CXCL12 / Q000276:immunology; D003106:Colon / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005512:Food Hypersensitivity / Q000276:immunology*; D006965:Hyperplasia; D007422:Intestines / Q000276:immunology / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D054834:Lipocalins / Q000235:genetics*; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010047:Ovalbumin; D015230:Prostaglandin D2 / Q000172:deficiency / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D054834:Lipocalins; C041524:aluminum sulfate; D010047:Ovalbumin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2