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

Goudarzi, Houman; Kimura, Hirokazu; Kimura, Hiroki et al.

Respiratory Research, 2022, 23(1), 174

Permalink : https://hdl.handle.net/2115/86799

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https://doi.org/10.1186/s12931-022-02038-1     1

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アクセス権
metadata only access
URI
https://hdl.handle.net/2115/86799
タイトル
Effects of obesity on CC16 and their potential role in overweight/obese asthma
著者
Goudarzi, Houman ; Kimura, Hirokazu ; Kimura, Hiroki ; Makita, Hironi ; Matsumoto, Munehiro ; Takei, Nozomu ; Shimizu, Kaoruko ; Suzuki, Masaru ; Watanabe, Taku ; Kikuchi, Eiki ; Ohira, Hiroshi ; Tsujino, Ichizo ; Sakakibara-Konishi, Jun ; Shinagawa, Naofumi ; Shijubo, Noriharu ; Sato, Hirokazu ; Shigehara, Katsunori ; Kaga, Kichizo ; Hida, Yasuhiro ; Murakami, Soichi ; Ebihara, Yuma ; Nakamura, Akinobu ; Miyoshi, Hideaki ; Hirano, Satoshi ; Hizawa, Nobuyuki ; Atsumi, Tatsuya ; Huang, Shau-ku ; Ito, Yoichi M. ; Nishimura, Masaharu ; Konno, Satoshi
著者名
Goudarzi, Houman
著者名
Kimura, Hirokazu
著者名
Kimura, Hiroki
著者名
Makita, Hironi
著者名
Matsumoto, Munehiro
著者名
Takei, Nozomu
著者名
Shimizu, Kaoruko
著者名
Suzuki, Masaru
著者名
Watanabe, Taku
著者名
Kikuchi, Eiki
著者名
Ohira, Hiroshi
著者名
Tsujino, Ichizo
著者名
Sakakibara-Konishi, Jun
著者名
Shinagawa, Naofumi
著者名
Shijubo, Noriharu
著者名
Sato, Hirokazu
著者名
Shigehara, Katsunori
著者名
Kaga, Kichizo
著者名
Hida, Yasuhiro
著者名
Murakami, Soichi
著者名
Ebihara, Yuma
著者名
Nakamura, Akinobu
著者名
Miyoshi, Hideaki
著者名
Hirano, Satoshi
著者名
Hizawa, Nobuyuki
著者名
Atsumi, Tatsuya
著者名
Huang, Shau-ku
著者名
Ito, Yoichi M.
著者名
Nishimura, Masaharu
e-Rad_Researcher
20399835
著者名
Konno, Satoshi
言語
英語
キーワード
CC16
Overweight and obesity
BMI
Asthma
Clinical asthma measures
発行日
2022-06-29
出版者
BioMed Central
収録物名
Respiratory Research
巻(号)
23(1)
ページ
174
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1186/s12931-022-02038-1