{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:47:02Z","timestamp":1787017622194,"version":"build-2736575974"},"reference-count":68,"publisher":"American Physiological Society","issue":"1","funder":[{"name":"Social Science and Technology Research Project of Zhongshan","award":["2018B1001"],"award-info":[{"award-number":["2018B1001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802031"],"award-info":[{"award-number":["81802031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771286"],"award-info":[{"award-number":["31771286"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2018A030310074"],"award-info":[{"award-number":["2018A030310074"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p>\n                    Asthma is a common heterogeneous respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR) which is associated with abnormality in smooth muscle contractility. The epithelial cell-derived cytokine IL-25 is implicated in type 2 immune pathology including asthma, whereas the underlying mechanisms have not been fully elucidated. This study aims to investigate the effects of IL-25 on mouse tracheal smooth muscle contractility and elucidate the cellular mechanisms. Incubation with IL-25 augmented the contraction of mouse tracheal smooth muscles, which could be suppressed by the L-type voltage-dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel (L-VDCC) blocker nifedipine. Furthermore, IL-25 enhanced the cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals and triggered the upregulation of \u03b11C L-VDCC (Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2) in primary cultured mouse tracheal smooth muscle cells. Knocking down IL-17RA\/IL-17RB receptors or inhibiting the transforming growth factor-\u03b2-activated kinase 1 (TAK1)-tumor progression locus 2 (TPL2)-MAPK kinase 1\/2 (MEK1\/2)-ERK1\/2-activating protein-1 (AP-1) signaling pathways suppressed the IL-25-elicited upregulation of Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 and hyperreactivity in tracheal smooth muscles. Moreover, inhibition of TPL2, ERK1\/2 or L-VDCC alleviated the AHR symptom induced by IL-25 in a murine model. This study revealed that IL-25 potentiated the contraction of tracheal smooth muscle and evoked AHR via activation of TPL2-ERK1\/2-Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 signaling, providing novel targets for the treatment of asthma with a high-IL-25 phenotype.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00468.2021","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T15:59:45Z","timestamp":1652198385000},"page":"L27-L36","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Cellular mechanism underlying the facilitation of contractile response induced by IL-25 in mouse tracheal smooth muscle"],"prefix":"10.1152","volume":"323","author":[{"given":"Ze-Xin","family":"Huang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Sun Yat-sen University, Guangzhou, People\u2019s Republic of 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