title: Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma.
abstract: Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA challenge, consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target.
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ikezoe
authors.affiliation: Department of Respiratory Care and Sleep Control Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Oga
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.|Center for Innovation in Immunoregulative Technology and Therapeutics (AK project), Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.|Center for Innovation in Immunoregulative Technology and Therapeutics (AK project), Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara-Chikuma
authors.affiliation: Core Research for Evolutional Science and Technology (CREST) Laboratory, Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Center for anatomical, forensic and pathology research, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.affiliation: Louis Pasteur Center for Medical Research, Sakyo-ku, Kyoto 606-8225, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Uno
authors.affiliation: Bioresearch Center, CMIC Pharma Science Co., Ltd., Hokuto-shi, Yamanashi 408-0044, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Fuchikami
authors.affiliation: Department of Respiratory Care and Sleep Control Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Tanizawa
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Handa
authors.affiliation: Department of Respiratory Medicine, Tenri Hospital, Tenri-shi, Nara 632-8552, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taguchi
authors.affiliation: Departments of Medicine and Physiology, University of California, San Francisco, CA 94143, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Verkman
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics (AK project), Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
authors.affiliation: Department of Respiratory Care and Sleep Control Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001249:Asthma / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002452:Cell Count; D002463:Cell Membrane Permeability; D018925:Chemokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000378:metabolism; D006967:Hypersensitivity / Q000150:complications / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D011014:Pneumonia / Q000150:complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000473:pathology
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D051400:Aquaporin 3; D010047:Ovalbumin; D006861:Hydrogen Peroxide