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Sci Rep. 2016 May 11;6:25781. doi: 10.1038/srep25781.

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

Author information

1
Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
2
Department of Respiratory Care and Sleep Control Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
3
Department of Dermatology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
4
Center for Innovation in Immunoregulative Technology and Therapeutics (AK project), Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
5
Core Research for Evolutional Science and Technology (CREST) Laboratory, Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
6
Center for anatomical, forensic and pathology research, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8501, Japan.
7
Louis Pasteur Center for Medical Research, Sakyo-ku, Kyoto 606-8225, Japan.
8
Bioresearch Center, CMIC Pharma Science Co., Ltd., Hokuto-shi, Yamanashi 408-0044, Japan.
9
Department of Respiratory Medicine, Tenri Hospital, Tenri-shi, Nara 632-8552, Japan.
10
Departments of Medicine and Physiology, University of California, San Francisco, CA 94143, USA.

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.

PMID:
27165276
PMCID:
PMC4863152
DOI:
10.1038/srep25781
[Indexed for MEDLINE]
Free PMC Article

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