2. Academic Validation
  3. Fezakinumab Alleviates Cigarette Smoke-Induced COPD by Suppressing the JAK1/STAT3 Pathway in Mice

Fezakinumab Alleviates Cigarette Smoke-Induced COPD by Suppressing the JAK1/STAT3 Pathway in Mice

  • Can Respir J. 2025 Nov 29:2025:3204642. doi: 10.1155/carj/3204642.
Yuwei Wang 1,  Li Jin 2,  Erche Yang 3,  Xiaoqun Niu 4,  Jianchuan Mao 1,  Chaoqun Yuan 1,  Yong Wang 1,  Bo You 1,  Lan Liu 1,  Yanling Chai 4
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, People's Hospital of Yuechi County, Yuechi, Sichuan 638300, China.
  • 2 Department of Anesthesiology, People's Hospital of Yuechi County, Yuechi, Sichuan 638300, China.
  • 3 Department of Respiratory and Critical Care Medicine, Dali Bai Autonomous Prefecture People's Hospital, Dali, Yunnan 671000, China.
  • 4 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
PMID: 41357311 DOI: 10.1155/carj/3204642
Abstract

Background: Elevated Th-22 cells and IL-22 are linked to chronic obstructive pulmonary disease (COPD); however, their mechanisms are not fully elucidated. This study aimed to evaluate the therapeutic effects of AG490 and fezakinumab in a cigarette smoke-induced COPD mouse model.

Methods: Cigarette smoke-induced COPD mice were divided into Air, CS, AG490, and Fezakinumab groups. We assessed BALF TH-22 cell levels, IL-22 levels and lung tissue (lung tissue were taken from the same anatomical site of the left lower lobe) histopathological changes, IL-22R1 expression, and protein expression of JAK1, Tyk2, STAT3, p-STAT3, Caspase3, Bax, and Bcl-2.

Results: Th-22 and IL-22 expressions were higher in the CS group than those in the Air group. Both the AG490 and Fezakinumab groups had reduced levels compared with the CS group but remained higher than the Air group. Similarly, IL-22R1 expression was higher in the CS group than in the Air group, while both AG490 and Fezakinumab groups exhibited lower expression than the CS group. H&E staining indicated less severe airway remodeling, alveolar enlargement, and inflammatory cell infiltration in the AG490 and Fezakinumab groups compared with the CS group. Western blot analysis revealed higher levels of JAK1, p-STAT3, and Caspase3 and lower levels of STAT3 and Bcl-2 in the CS group than those in the Air group. Both AG490 and Fezakinumab groups exhibited lower levels of JAK1, p-STAT3, and Caspase3 than the CS group, while Fezakinumab groups exhibited lower levels of STAT3 and higher levels of Bcl-2 than the CS group.

Conclusions: Th-22 cells and IL-22 play crucial roles in COPD pathogenesis. Fezakinumab and AG490 mitigate airway remodeling, alveolar enlargement, and pulmonary tissue inflammatory cell infiltration by modulating JAK/STAT pathways and Apoptosis. These results suggest promising targeted therapies for COPD, potentially improving patient outcomes by addressing inflammatory mechanisms.

Keywords

AG490; IL-22,COPD; JAK/STAT pathway; apoptosis; fezakinumab.

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