title: Production of interleukin (IL)-33 in the lungs during multiple antigen challenge-induced airway inflammation in mice, and its modulation by a glucocorticoid.
abstract: Although interleukin (IL)-33 is a candidate aggravator of asthma, the cellular sources of IL-33 in the lungs during the progression of antigen-induced airway inflammation remain unclear. Furthermore, it has not been determined whether the antigen-induced production of IL-33 can be pharmacologically modulated in vivo. In this study, we examined the production of IL-33 in the lungs of sensitized mice during multiple intratracheal challenges with the antigen, ovalbumin. The 1st challenge clearly induced the IL-33 production in the lungs, and it was enhanced by the 2nd-4th challenges. IL-33 mRNA transcription was also induced after these challenges. An immunohistochemical analysis revealed that the cellular sources of IL-33 after the 1st challenge were mainly bronchial epithelial cells, while those after the 3rd challenge were not only the epithelial cells, but also inflammatory cells that infiltrated the lungs. Flow cytometric analyses indicated that approximately 20% and 10% of the IL-33-producing cells in the lungs were M2 macrophages and conventional dendritic cells, respectively. A systemic treatment with dexamethasone before the 1st challenge potently suppressed the IL-33 production. When dexamethasone was administered before the respective challenges, production of the IL-33 protein and the infiltration of IL-33-producing M2 macrophages and dendritic cells into the lungs in the 3rd challenge were also suppressed. In conclusion, the cellular sources of IL-33 in the lungs were dynamically altered during multiple challenges: not only bronchial epithelial cells, but also the M2 macrophages and dendritic cells that infiltrated the lungs produced IL-33. The production of IL-33 was susceptible to the glucocorticoid treatment.
authors: Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan; Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. Electronic address: t-nabe@pharm.setsunan.ac.jp.
authors: Takeshi
authors: T
authors: Nabe
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Hiroki
authors: H
authors: Wakamori
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Chihiro
authors: C
authors: Yano
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Ayumi
authors: A
authors: Nishiguchi
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Rino
authors: R
authors: Yuasa
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Hitomi
authors: H
authors: Kido
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Yusaku
authors: Y
authors: Tomiyama
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Ayumi
authors: A
authors: Tomoda
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Haruka
authors: H
authors: Kida
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Anna
authors: A
authors: Takiguchi
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Masaya
authors: M
authors: Matsuda
authors: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Keiichi
authors: K
authors: Ishihara
authors: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Satoshi
authors: S
authors: Akiba
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Susumu
authors: S
authors: Ohya
authors: Department of Molecular Studies for Incurable Diseases, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
authors: Hiroyuki
authors: H
authors: Fukui
authors: Department of Pharmacology, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors: Nobuaki
authors: N
authors: Mizutani
authors: Department of Pharmacology, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors: Shin
authors: S
authors: Yoshino
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000096:biosynthesis* / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology
chemical_list: D000941:Antigens; D005938:Glucocorticoids; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D003907:Dexamethasone; D010047:Ovalbumin
keywords: Asthma; Dendritic cells; Epithelial cells; Glucocorticoid; Interleukin-33; M2 macrophages