RRC ID 34566
Author Nakamura T, Maeda S, Horiguchi K, Maehara T, Aritake K, Choi BI, Iwakura Y, Urade Y, Murata T.
Title PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia.
Journal Nat Commun
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.
Volume 6
Pages 7514
Published 2015-7-10
DOI 10.1038/ncomms8514
PII ncomms8514
PMID 26159556
MeSH Adjuvants, Immunologic Alum Compounds Animals Chemokine CXCL12 / immunology Colon / immunology* Colon / pathology Cytokines / immunology Enzyme-Linked Immunosorbent Assay Food Hypersensitivity / immunology* Hyperplasia Intestines / immunology Intestines / pathology Intramolecular Oxidoreductases / genetics* Lipocalins / genetics* Mast Cells / immunology* Mast Cells / pathology Matrix Metalloproteinase 9 / immunology Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Electron Ovalbumin Prostaglandin D2 / deficiency Prostaglandin D2 / immunology* Reverse Transcriptase Polymerase Chain Reaction
IF 12.121
Times Cited 16
Mice RBRC01888