{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:57:53Z","timestamp":1772517473938,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"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>Interferon-\u03b3 (IFN\u03b3), a key inflammatory cytokine that orchestrates immune responses, also emerges as a regulator of cellular metabolism; however, in alveolar epithelial cells its impact on amino acid homeostasis remains poorly defined. Here, we investigated the effects of IFN\u03b3 on intracellular amino acid content and transmembrane transport in human alveolar epithelial A549 cells, focusing on the contribution of the JAK\/STAT\/IRF1 signaling axis. To this end, A549 WT and IRF1 knockout (IRF1 KO) cells were used to investigate IRF1 contribution, and baricitinib to evaluate the role of the JAK\/STAT pathway. HPLC analysis reveals that in WT, but not in IRF1 KO cells, IFN\u03b3 markedly increases the intracellular concentration of many amino acids, including glutamine, glutamate, and several neutral and cationic amino acids, without affecting the cell volume, thus indicating true metabolic accumulation. The measurement of the transmembrane uptake of specific radiolabeled amino acids demonstrates a concomitant increase in transport Systems ASC, A, L, and y+ activity; an upregulation of the related transporters ASCT2, SNAT2, LAT1, and CAT1 has also been observed by means of qPCR analysis. Moreover, conditioned medium from SARS-CoV-2 spike-activated macrophages recapitulates IFN\u03b3-driven amino acid remodeling in a JAK\/STAT\/IRF1-dependent manner. Overall, our findings identify IFN\u03b3 as a potent regulator of intracellular amino acid availability in alveolar epithelial cells through the modulation of the activity of membrane transporters. The observed IFN\u03b3-reprogramming is IRF1 dependent, ascribing a crucial role to this transcription factor in linking inflammation and amino acid metabolism.<\/jats:p>","DOI":"10.3390\/ijms27052220","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"2220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IFN\u03b3 Increases Intracellular Amino Acid Content in Human Alveolar Epithelial Cells: Role of the STAT\/IRF1 Axis in the Stimulation of Transmembrane Transport"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2256-0530","authenticated-orcid":false,"given":"Amelia","family":"Barilli","sequence":"first","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"Visigalli","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8727-6227","authenticated-orcid":false,"given":"Eleonora","family":"Crescini","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-7783","authenticated-orcid":false,"given":"Giulia","family":"Recchia Luciani","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, S., Carriere, J., Lin, X., Xie, N., and Feng, P. 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