{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:07:38Z","timestamp":1788962858039,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp; Disease"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dexmedetomidine (DEX) is primarily utilized for sedation in the context of general anesthesia or intensive care. However, the exact regulatory mechanism by which DEX affects cytokines remains unclear. This study aims to investigate the underlying mechanism by which DEX inhibits proinflammatory factors through activation of the \u03b22 adrenergic receptor (\u03b22 AR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The inflammatory cell model of human mononuclear macrophage (THP\u20101) cells induced by lipopolysaccharide (LPS) was established to study the effect of DEX on the expression of cell\u2010related inflammatory factors. ADRA2A gene knockout THP\u20101 cells (THP\u20101\n                      <jats:sup>KO<\/jats:sup>\n                      ) were constructed by CRISPR technology, and the effect of DEX on the expression of inflammatory factors of THP\u20101\n                      <jats:sup>KO<\/jats:sup>\n                      cells was detected. The target sites of DEX on \u03b22 AR were screened by molecular docking. Reversion experiments were performed using ADRB2\u2010siRNA. Western blot was used to detect the activation of \u03b22 AR\/PKA\/CREB pathway and NF\u2010\u03baB, and ELISA was used to detect the release level of inflammatory factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results demonstrated a significant reduction in the expression levels of MCP\u20101, interleukin\u201006, and IL\u20108 in both THP\u20101 and THP\u20101\n                      <jats:sup>KO<\/jats:sup>\n                      cells when induced by LPS following treatment with DEX. Additionally, DEX treatment led to an increase in IL\u201010 expression. Immunofluorescence analysis revealed an upregulation of \u03b22 AR expression after DEX treatment. Western blot results indicated that DEX notably enhanced the activation of the \u03b22 AR and PKA\/CREB pathways, while concurrently suppressing the activation of NF\u2010\u03baB. Notably, the use of ADRB2 siRNA reversed the effects of DEX treatment and promoted the release of inflammatory cytokines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DEX initiates the activation of the PKA\/CREB pathway through the activation of \u03b22 AR. Simultaneously, it exerts an inhibitory effect on the activation of NF\u2010\u03baB, consequently reducing the transcription of proinflammatory factors while increasing the transcription of anti\u2010inflammatory factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.1176","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T07:39:34Z","timestamp":1709019574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dexmedetomidine activates the PKA\/CREB pathway and inhibits proinflammatory factor expression through \u03b22 adrenergic receptors"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-6518","authenticated-orcid":false,"given":"Baocheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Emergency and Critical Care Center Jinshan Hospital Affiliated to Fudan University Shanghai 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