{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:42:00Z","timestamp":1792618920430,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In COVID-19, cytokine release syndrome can cause severe lung tissue damage leading to acute respiratory distress syndrome (ARDS). Here, we address the effects of IFN\u03b3, TNF\u03b1, IL-1\u03b2 and IL-6 on the growth arrest of alveolar A549 cells, focusing on the role of the IFN regulatory factor 1 (IRF1) transcription factor. The efficacy of JAK1\/2 inhibitor baricitinib has also been tested. A549 WT and IRF1 KO cells were exposed to cytokines for up to 72 h. Cell proliferation and death were evaluated with the resazurin assay, analysis of cell cycle and cycle-regulator proteins, LDH release and Annexin-V positivity; the induction of senescence and senescence-associated secretory phenotype (SASP) was evaluated through \u03b2-galactosidase staining and the quantitation of secreted inflammatory mediators. While IL-1 and IL-6 proved ineffective, IFN\u03b3 plus TNF\u03b1 caused a proliferative arrest in A549 WT cells with alterations in cell morphology, along with the acquisition of a secretory phenotype. These effects were STAT and IRF1-dependent since they were prevented by baricitinib and much less evident in IRF1 KO than in WT cells. In alveolar cells, STATs\/IRF1 axis is required for cytokine-induced proliferative arrest and the induction of a secretory phenotype. Hence, baricitininb is a promising therapeutic strategy for the attenuation of senescence-associated inflammation.<\/jats:p>","DOI":"10.3390\/ijms25063463","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T09:39:31Z","timestamp":1710841171000},"page":"3463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFN\u03b3\/TNF\u03b1"],"prefix":"10.3390","volume":"25","author":[{"given":"Giulia","family":"Recchia Luciani","sequence":"first","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Barilli","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Visigalli","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9167-0020","authenticated-orcid":false,"given":"Roberto","family":"Sala","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-0916","authenticated-orcid":false,"given":"Valeria","family":"Dall\u2019Asta","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Maria","family":"Rotoli","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/imr.12671","article-title":"Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology","volume":"285","author":"Cicchese","year":"2018","journal-title":"Immunol. 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