{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:53:36Z","timestamp":1780408416789,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["AI158886"],"award-info":[{"award-number":["AI158886"]}],"id":[{"id":"10.13039\/100017540","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":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sedatives\/anesthetics are important medical tools to facilitate medical care and increase patients' comfort. Increasingly, there is recognition that sedatives\/anesthetics can modulate immune functions. Toll\u2010like receptors (TLRs) are major pattern recognition receptors involved in the recognition of microbial components. TLR7 recognizes single\u2010strand RNA virus such as influenza and SARS\u2010CoV2 viruses and initiates interferon (IFN) responses. IFN production triggered by TLR7 stimulation is a critical anti\u2010viral response. For example, patients with TLR7 variants including loss\u2010of\u2010 function variants were associated with severe COVID\u201019. Taken together, it is important to determine if sedatives\/anesthetics mitigate TLR7 function. We have previously showed that TLR7\u2010mediated activation was not affected by volatile anesthetics. However, we found that propofol attenuated TLR7 activation among intravenous sedatives in the reporter assay. TLR7 agonist R837 stimulation increased TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106, IL\u201010, and IFN\u2010\u03b2 mRNA levels in bone marrow\u2010derived dendritic cells, while these levels were attenuated by propofol. Our murine lung slice experiments showed that propofol attenuated IFN production. R837 increased IFN\u2010\u03b2 expression in the lungs, and propofol attenuated IFN\u2010\u03b2 expression in an in vivo model of R837 intranasal instillation. We also found that propofol directly bound to and hindered its association of TLR7 with MyD88. Our analysis using fropofol, propofol derivative showed that the hydroxyl group in propofol was important for propofol\u2013TLR7 interaction.<\/jats:p>","DOI":"10.1096\/fj.202200312r","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T03:58:28Z","timestamp":1658980708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Propofol directly binds to and inhibits\n                    <scp>TLR7<\/scp>"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3555-1681","authenticated-orcid":false,"given":"Sophia","family":"Koutsogiannaki","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Department of Anaesthesia and Immunology Harvard Medical School  Boston Massachusetts 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