title: Expression and effects of IL-33 and ST2 in allergic bronchial asthma: IL-33 induces eotaxin production in lung fibroblasts.
abstract: BACKGROUND
  Interleukin (IL)-33, a new member of the IL-1 cytokine family, has been recognized as a key cytokine that enhances T helper 2-balanced immune regulation through its receptor ST2; however, the function and relationship of the IL-33 and ST2 pathways in bronchial asthma are still unclear. We investigated the cellular origin and regulation of IL-33 and ST2 in allergic bronchial asthma in vivo and in vitro.
  
  
  METHODS
  BALB/c mice were sensitized by intraperitoneal injections of ovalbumin (OVA) with alum. Mice were exposed to aerosolized 1% OVA for 30 min a day for 7 days. These mice were then challenged with aerosolized 1% OVA 2 days after the last day of exposure. After the OVA challenge, the mice were sacrificed and their lung tissues were obtained. Mouse lung fibroblasts were cultured and treated with IL-33 or IL-13.
  
  
  RESULTS
  The levels of IL-33 mRNA and IL-33 protein in lung tissue increased after the OVA challenge. Most IL-33-expressing cells were CD11c+ cells and epithelial cells, and many ST2-expressing cells were stained lung fibroblasts and inflammatory cells. IL-33 induced eotaxin/CCL11 production in lung fibroblasts. IL-33 and IL-13 synergistically induced eotaxin expression.
  
  
  CONCLUSIONS
  IL-33 may contribute to the induction and maintenance of eosinophilic inflammation in the airways by acting on lung fibroblasts. IL-33 and ST2 may play important roles in allergic bronchial asthma.
authors.affiliation: Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. cdl94140@par.odn.ne.jp
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsukura
authors.forename: Mio
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Koushi
authors.initials: K
authors.lastname: Ieki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Suzuki
authors.forename: Miho
authors.initials: M
authors.lastname: Odaka
authors.forename: Shin
authors.initials: S
authors.lastname: Watanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Homma
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sato
authors.forename: Munehiro
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D014746:Vimentin; D010047:Ovalbumin