{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:50:24Z","timestamp":1791280224936,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000032","name":"Institute of Infection and Immunity","doi-asserted-by":"publisher","award":["PJT\u2010178398"],"award-info":[{"award-number":["PJT\u2010178398"]}],"id":[{"id":"10.13039\/501100000032","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The nucleocapsid (N) protein of SARS\u2010CoV\u20102 is critical for viral replication and genome packaging. However, whether it induces inflammation through endothelial cell and monocyte activation remains controversial. One aspect that has been overlooked is the consideration of residual endotoxins in recombinant proteins when conducting immune response studies. We aimed to assess whether N\u2010protein induces an inflammatory response in mouse and human microvascular endothelial cells (MEC and HMEC) and THP\u20101 cells, independent of endotoxin contamination. MEC, HMEC, and THP\u20101 cells were treated with vehicle, lipopolysaccharide (LPS), or recombinant N\u2010protein in the presence or absence of the LPS\u2010neutralizing agent polymyxin B. The inflammatory response was assessed through quantification of mRNA and protein levels of inflammatory markers and monocyte adhesion to endothelial cells. In MEC, treatment with N\u2010protein resulted in at least a 15\u2010fold increase in inflammatory marker levels. Similarly, in THP\u20101 cells, N\u2010protein caused a significant increase in mRNA inflammatory marker levels, which were brought back to control levels with polymyxin B. LPS or N\u2010protein alone resulted in a tripling of monocyte adhesion to MEC, and this was reduced to control levels with polymyxin B. In addition, in HMEC, endotoxin\u2010depleted N\u2010protein did not cause a significant increase in inflammatory marker levels. In conclusion, our data show that N\u2010protein does not induce inflammation in endothelial cells or monocytes. Some of its observed inflammatory effects may be due to endotoxin contamination, suggesting that it does not directly induce inflammation.<\/jats:p>","DOI":"10.1096\/fj.202501433r","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T14:54:55Z","timestamp":1761144895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 Nucleocapsid Protein Does Not Induce Inflammation in Endothelial Cells or Monocytes"],"prefix":"10.1096","volume":"39","author":[{"given":"Mehreen","family":"Tufail","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry Western University  London Ontario 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