title: Augmentation of allergic inflammation in prostanoid IP receptor deficient mice.
abstract: 1 To evaluate the role of prostaglandin I(2) (PGI(2)) in allergic inflammation, allergic responses in the airway, skin and T cells were studied in mice lacking the receptor for PGI(2) (the prostanoid IP receptor) through gene disruption. 2 Three inhalations of antigen caused an increase in plasma extravasation, leukocyte accumulation and cytokine (interleukin (IL)-4 and IL-5) production in the airway of sensitized mice. These airway inflammatory responses were significantly greater in IP receptor deficient mice than in wild-type mice. 3 The vascular leakage caused by passive cutaneous anaphylaxis, substance P and 5-hydroxytryptamine was markedly increased in the skin of IP receptor deficient mice, compared with comparably treated wild-type mice. 4 The inhalation of antigen in sensitized mice resulted in increased serum antigen specific IgE, total IgE and IgG levels. The magnitude of the elevations of each immunoglobulin level in IP receptor deficient mice is notably higher than that in wild-type mice. To elucidate the mechanism of an enhancement of immunoglobulin production, the activity of T cells in sensitized and non-sensitized mice was studied by means of the production of cytokines. The antigen-induced IL-4 production by spleen cells from sensitized IP receptor deficient mice was almost three times greater than that in wild-type mice. On the contrary, the anti-CD3 antibody-induced interferon-gamma production by CD4(+) T cells from non-sensitized IP receptor deficient mice was significantly lower than that in wild-type mice. 5 The present data indicate that IP receptor deficiency reinforced an allergic airway and skin inflammation by augmentation of vascular permeability increase and the T helper 2 cell function. These findings suggest a regulatory role of PGI(2) in allergic inflammation.
authors.affiliation: Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shota
authors.initials: S
authors.lastname: Tokuoka
authors.forename: Taisei
authors.initials: T
authors.lastname: Masuda
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Hirano
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nagao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability; D016207:Cytokines / Q000096:biosynthesis; D011464:Epoprostenol / Q000502:physiology*; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000172:deficiency* / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; C491910:Ptgir protein, mouse; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D007073:Immunoglobulin E; D011464:Epoprostenol