{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T18:05:54Z","timestamp":1775066754573,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006364","name":"French National Cancer Institute","doi-asserted-by":"publisher","award":["INCa_13641"],"award-info":[{"award-number":["INCa_13641"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1\u03b2 (IL-1\u03b2) and Tumor Necrosis Factor a (TNF\u03b1), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1\u03b2, and TNF\u03b1 is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management.<\/jats:p>","DOI":"10.3390\/ijms23031911","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:37:48Z","timestamp":1644363468000},"page":"1911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["AKR1B10, One of the Triggers of Cytokine Storm in SARS-CoV2 Severe Acute Respiratory Syndrome"],"prefix":"10.3390","volume":"23","author":[{"given":"Clovis","family":"Chabert","sequence":"first","affiliation":[{"name":"Institute for Advanced Biosciences\u2014UGA\u2014INSERM U1209\u2014CNRS UMR 5309, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-7673","authenticated-orcid":false,"given":"Anne-Laure","family":"Vitte","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences\u2014UGA\u2014INSERM U1209\u2014CNRS UMR 5309, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Iuso","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences\u2014UGA\u2014INSERM U1209\u2014CNRS UMR 5309, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florent","family":"Chuffart","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences\u2014UGA\u2014INSERM U1209\u2014CNRS UMR 5309, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice","family":"Trocme","sequence":"additional","affiliation":[{"name":"Laboratoire BEP (Biochimie des Enzymes et les Prot\u00e9ines), Institut de Biologie et de Pathologie, CHU Grenoble Alpes, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlyse","family":"Buisson","sequence":"additional","affiliation":[{"name":"Institut de Biologie Structurale, CEA, CNRS and Centre Hospitalier Universitaire Grenoble Alpes, Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Poignard","sequence":"additional","affiliation":[{"name":"Institut de Biologie Structurale, CEA, CNRS and Centre Hospitalier Universitaire Grenoble Alpes, Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-1196","authenticated-orcid":false,"given":"Benjamin","family":"Lardinois","sequence":"additional","affiliation":[{"name":"Laboratory Department, CHU UCL Namur Site de Ste Elisabeth, 5000 Namur, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9gis","family":"Debois","sequence":"additional","affiliation":[{"name":"Laboratory Department, CHU UCL Namur Site de Ste Elisabeth, 5000 Namur, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5246-5350","authenticated-orcid":false,"given":"Sophie","family":"Rousseaux","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences\u2014UGA\u2014INSERM U1209\u2014CNRS UMR 5309, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Louis","family":"Pepin","sequence":"additional","affiliation":[{"name":"HP2 Laboratory, INSERM U1300, Grenoble Alpes University, 38000 Grenoble, France"},{"name":"Sleep Laboratory, Pole Thorax et Vaisseaux, Grenoble Alpes University Hospital, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Benoit","family":"Martinot","sequence":"additional","affiliation":[{"name":"Sleep Laboratory and Pulmonology and Allergy Department\u2014CHU UCL Namur, St. Elisabeth Site, 5000 Namur, Belgium"},{"name":"Institute of Experimental and Clinical Research, UCL Bruxelles Woluwe, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saadi","family":"Khochbin","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences\u2014UGA\u2014INSERM U1209\u2014CNRS UMR 5309, 38700 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","unstructured":"(2022, January 12). 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