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Effects of obesity on CC16 and their potential role in overweight/obese asthma

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Title: Effects of obesity on CC16 and their potential role in overweight/obese asthma
Authors: Goudarzi, Houman Browse this author
Kimura, Hirokazu Browse this author
Kimura, Hiroki Browse this author
Makita, Hironi Browse this author
Matsumoto, Munehiro Browse this author
Takei, Nozomu Browse this author
Shimizu, Kaoruko Browse this author
Suzuki, Masaru Browse this author
Watanabe, Taku Browse this author
Kikuchi, Eiki Browse this author
Ohira, Hiroshi Browse this author
Tsujino, Ichizo Browse this author
Sakakibara-Konishi, Jun Browse this author
Shinagawa, Naofumi Browse this author
Shijubo, Noriharu Browse this author
Sato, Hirokazu Browse this author
Shigehara, Katsunori Browse this author
Kaga, Kichizo Browse this author
Hida, Yasuhiro Browse this author
Murakami, Soichi Browse this author
Ebihara, Yuma Browse this author
Nakamura, Akinobu Browse this author
Miyoshi, Hideaki Browse this author
Hirano, Satoshi Browse this author
Hizawa, Nobuyuki Browse this author
Atsumi, Tatsuya Browse this author
Huang, Shau-ku Browse this author
Ito, Yoichi M. Browse this author
Nishimura, Masaharu Browse this author
Konno, Satoshi Browse this author →KAKEN DB
Keywords: CC16
Overweight and obesity
Clinical asthma measures
Issue Date: 29-Jun-2022
Publisher: BioMed Central
Journal Title: Respiratory Research
Volume: 23
Issue: 1
Start Page: 174
Publisher DOI: 10.1186/s12931-022-02038-1
Abstract: Introduction Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. Methods Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. Results BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI's association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001). Conclusions We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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