{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:55:39Z","timestamp":1791939339423,"version":"4.3.4"},"reference-count":84,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSF Collaborative Research","award":["2031754"],"award-info":[{"award-number":["2031754"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the \u201cCytokine Storm\u201d, which is a dramatic increase in inflammatory cytokines in the blood. In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or \u201cLong COVID\u201d. Therefore, there is an urgent need to better understand the mechanisms of the virus. The spike protein on the surface of the virus is composed of joined S1\u2013S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and\/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.<\/jats:p>","DOI":"10.3390\/microorganisms10101996","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T23:31:43Z","timestamp":1665358303000},"page":"1996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-7751","authenticated-orcid":false,"given":"Christopher B.","family":"Forsyth","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Gastroenterology, Rush Center for Integrated Microbiome and Chronobiology Research, Department of Anatomy and Cell Biology, Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-9005","authenticated-orcid":false,"given":"Abhinav","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-5720","authenticated-orcid":false,"given":"Barbara","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Adult Health & Gerontological Nursing, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-1876","authenticated-orcid":false,"given":"Jo\u00e3o I.","family":"Mamede","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M.","family":"Voigt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gastroenterology, Rush Center for Integrated Microbiome and Chronobiology Research, Department of Anatomy and Cell Biology, Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maliha","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A.","family":"Engen","sequence":"additional","affiliation":[{"name":"Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Keshavarzian","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gastroenterology, Rush Center for Integrated Microbiome and Chronobiology Research, Department of Anatomy and Cell Biology, Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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