{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:43:30Z","timestamp":1784547810344,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intestinal muscularis resident macrophages (MM\u03c6) are a specialized subset of tissue macrophages involved in local inflammatory regulation. Although sympathetic nerves are anatomically associated with MM\u03c6, the mechanisms underlying their interaction remain unclear. This study aimed to elucidate the role of adrenergic receptor signaling in modulating MM\u03c6 activation during lipopolysaccharide (LPS)\u2010induced inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MM\u03c6 were isolated from mouse intestinal muscularis for receptor profiling. The macrophage\u2010like cell line J774.1 was stimulated with LPS, with or without adrenergic modulators. LPS\u2010treated intestinal segments were examined ex\u00a0vivo under electrical stimulation with sympathetic or\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010adrenergic blockade. Macrophage activation was assessed by measuring nitric oxide (NO) production and iNOS mRNA expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      MM\u03c6 isolated from mouse muscularis expressed \u03b1\u2081, \u03b1\u2082,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2081, and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2082 adrenergic receptors. In J774.1 cells, LPS significantly increased NO production. Activation of \u03b1\u2081,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2081, or\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2082 receptors attenuated this response, whereas \u03b1\u2082 activation enhanced it. Norepinephrine similarly suppressed LPS\u2010induced NO increase, and this suppression was reversed by\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2081\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2082 antagonists. Inhibition of adenylate cyclase also reversed the NO suppression induced by a non\u2010selective\n                      <jats:italic>\u03b2<\/jats:italic>\n                      receptor agonist. In intestinal segments, LPS\u2010induced iNOS expression was not altered by electrical stimulation, but was significantly enhanced when stimulation was combined with non\u2010selective\n                      <jats:italic>\u03b2<\/jats:italic>\n                      or\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2081 antagonists.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Inferences<\/jats:title>\n                    <jats:p>\n                      Our results suggest that norepinephrine released from sympathetic nerves suppresses inflammation via activation of\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2081 and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2082 receptors on MM\u03c6. These findings advance the understanding of neuroimmune interactions underlying gastrointestinal homeostasis and its disruption during inflammatory states.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70285","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:06:32Z","timestamp":1773133592000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sympathetic Norepinephrine Modulates Inflammatory Activation in Intestinal Muscularis Resident Macrophages via Beta1\u2010Adrenergic Receptors"],"prefix":"10.1111","volume":"38","author":[{"given":"Tomo","family":"Fukuda","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine Azabu University  Azabu Kanagawa 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