{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:49:03Z","timestamp":1771026543590,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,6]],"date-time":"2015-01-06T00:00:00Z","timestamp":1420502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation grants of China","doi-asserted-by":"crossref","award":["81370110"],"award-info":[{"award-number":["81370110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation Project of Chongqing","award":["CSTC 2011jjA10063"],"award-info":[{"award-number":["CSTC 2011jjA10063"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Airway inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are associated with elevated expression of interleukin\u201032 (IL\u201032), a recently described cytokine that appears to play a critical role in inflammation. However, so far, the regulation of pulmonary IL\u201032 production has not been fully established. We examined the expression of IL\u201032 by tumour necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (TNF\u2010<jats:italic>\u03b1<\/jats:italic>) in primary human lung fibroblasts. Human lung fibroblasts were cultured in the presence or absence of TNF\u2010<jats:italic>\u03b1<\/jats:italic> and\/or other cytokines\/Toll\u2010like receptor (TLR) ligands or various signalling molecule inhibitors to analyse the expression of IL\u201032 by quantitative RT\u2010PCR and ELISA. Next, activation of Akt and c\u2010Jun N\u2010terminal kinase (JNK) signalling pathways was investigated by Western blot. Interleukin\u201032 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> of four spliced isoforms (<jats:italic>\u03b1<\/jats:italic>,<jats:italic> \u03b2<\/jats:italic>,<jats:italic> \u03b3<\/jats:italic> and <jats:italic>\u03b4<\/jats:italic>) was up\u2010regulated upon TNF\u2010<jats:italic>\u03b1<\/jats:italic> stimulation, which was associated with a significant IL\u201032 protein release from TNF\u2010<jats:italic>\u03b1<\/jats:italic>\u2010activated human lung fibroblasts. The combination of interferon\u2010<jats:italic>\u03b3<\/jats:italic> and TNF\u2010<jats:italic>\u03b1<\/jats:italic> induced enhanced IL\u201032 release in human lung fibroblasts, whereas IL\u20104, IL\u201017A, IL\u201027 and TLR ligands did not alter IL\u201032 release in human lung fibroblasts either alone, or in combination with TNF\u2010<jats:italic>\u03b1<\/jats:italic>. Furthermore, the activation of Akt and JNK pathways regulated TNF\u2010<jats:italic>\u03b1<\/jats:italic>\u2010induced IL\u201032 expression in human lung fibroblasts, and inhibition of the Akt and JNK pathways was able to suppress the increased release of IL\u201032 to nearly the basal level. These data suggest that TNF\u2010<jats:italic>\u03b1<\/jats:italic> may be involved in airway inflammation via the induction of IL\u201032 by activating Akt and JNK signalling pathways. Therefore, the TNF\u2010<jats:italic>\u03b1<\/jats:italic>\/IL\u201032 axis may be a potential therapeutic target for airway inflammatory diseases.<\/jats:p>","DOI":"10.1111\/imm.12374","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T10:15:35Z","timestamp":1409048135000},"page":"282-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["c\u2010Jun N\u2010terminal kinase and Akt signalling pathways regulating tumour necrosis factor\u2010<i>\u03b1<\/i>\u2010induced interleukin\u201032 expression in human lung fibroblasts: implications in airway inflammation"],"prefix":"10.1111","volume":"144","author":[{"given":"Dagen","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education Chongqing Medical University Chongqing 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