Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma

• Published in: Scientific reports Vol. 6; no. 1; p. 25781
• Main Authors: Ikezoe, Kohei, Oga, Toru, Honda, Tetsuya, Hara-Chikuma, Mariko, Ma, Xiaojun, Tsuruyama, Tatsuaki, Uno, Kazuko, Fuchikami, Jun-ichi, Tanizawa, Kiminobu, Handa, Tomohiro, Taguchi, Yoshio, Verkman, Alan S., Narumiya, Shuh, Mishima, Michiaki, Chin, Kazuo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.05.2016; Nature Publishing Group
• Subjects: 13/31; 13/51; 38/61; 38/77; 631/250/1619/554/1898; 631/250/256/2516; 631/250/98; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep25781

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 (H 2 O 2 ). 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 H 2 O 2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma and AQP3 may be a novel therapeutic target.