Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation

Eun Young Heo, Kyoung Hee Lee, Jisu Woo, Jiyeon Kim, Chang Hoon Lee, Kyung Jin Lee, Yun Kyu Kim, Chul Gyu Yoo

Research output: Contribution to journalArticlepeer-review

Abstract

Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.

Original languageEnglish
Article number1980
JournalAntioxidants
Volume11
Issue number10
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • NF-κB
  • cereblon
  • emphysema
  • lung inflammation

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