{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:30:32Z","timestamp":1785331832571,"version":"3.55.0"},"reference-count":75,"publisher":"American Society for Clinical Investigation","issue":"15","funder":[{"name":"JSPS KAKENHI","award":["16H06272E,17KK0165,17K19747,19H03828,19K22706"],"award-info":[{"award-number":["16H06272E,17KK0165,17K19747,19H03828,19K22706"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DE024716,DE028561,DE026152"],"award-info":[{"award-number":["DE024716,DE028561,DE026152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB-TR 205,SFB1181"],"award-info":[{"award-number":["SFB-TR 205,SFB1181"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,6]]},"abstract":"<jats:p>\n                    Macrolide antibiotics exert antiinflammatory effects; however, little is known regarding their immunomodulatory mechanisms. In this study, using 2 distinct mouse models of mucosal inflammatory disease (LPS-induced acute lung injury and ligature-induced periodontitis), we demonstrated that the antiinflammatory action of erythromycin (ERM) is mediated through upregulation of the secreted homeostatic protein developmental endothelial locus-1 (DEL-1). Consistent with the anti\u2013neutrophil recruitment action of endothelial cell\u2013derived DEL-1, ERM inhibited neutrophil infiltration in the lungs and the periodontium in a DEL-1\u2013dependent manner. Whereas ERM (but not other antibiotics, such as josamycin and penicillin) protected against lethal pulmonary inflammation and inflammatory periodontal bone loss, these protective effects of ERM were abolished in\n                    <jats:italic>Del1<\/jats:italic>\n                    -deficient mice. By interacting with the growth hormone secretagogue receptor and activating JAK2 in human lung microvascular endothelial cells, ERM induced DEL-1 transcription that was mediated by MAPK p38 and was CCAAT\/enhancer binding protein\u2013\u03b2 dependent. Moreover, ERM reversed IL-17\u2013induced inhibition of DEL-1 transcription, in a manner that was dependent not only on JAK2 but also on PI3K\/AKT signaling. Because DEL-1 levels are severely reduced in inflammatory conditions and with aging, the ability of ERM to upregulate DEL-1 may lead to a novel approach for the treatment of inflammatory and aging-related diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.136706","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T15:00:39Z","timestamp":1593529239000},"source":"Crossref","is-referenced-by-count":30,"title":["Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-1316","authenticated-orcid":true,"given":"Tomoki","family":"Maekawa","sequence":"first","affiliation":[{"name":"Center for Advanced Oral Science,"},{"name":"Division of Microbiology and Infectious Diseases,"},{"name":"Division of Periodontology, 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