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

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

62016-05-11 , Nature Publishing Group
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.

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