Year: 2020
Type: article
Abstract: 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-neutrophil recruitment action of endothelial cell-derived DEL-1, ERM inhibited neutrophil infiltration in the lungs and the periodontium in a DEL-1-dependent 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 Del1-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-β dependent. Moreover, ERM reversed IL-17-induced 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.
Source: JCI Insight
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: New strategies for preventing undernutrition in the elderly-tailor-made nutrition guidance method tailored to denture guidance-, Elucidation of the TRP-TLR interaction in the pathogenesis of inflammatory diseases, エリスロマイシン改変体の抗炎症Del-1分子誘導による炎症性骨吸収制御法の検索, Elucidation of effectiveness and mechanism of new water-soluble glycolipids in bacterial pneumonia control, Therapeutic strategies against inflammation and bone loss associated with Del-1 production, G2045909891, Del-1: Molecular and Cellular Targets in Periodontitis, Challenges to the identification of neutrophil subsets involved in the development and remission of inflammation, Establishment and development of metagenomics-based priodontitis diagnostic platform, G3319228230, G3548458114, G5391660184, Next step in the oral-gut connection: Do swallowed periodontopathogenic bacteria exacerbate colitis?, Periodontal disease and the risk factors for atherosclerosis among subjects who received general medical check-ups, G692634027, Integrated understanding of Del-1 functions on osteobiology and Inflammation, Aging and dysfunction of progenitor niches: Role of Del-1, G7631702783, G7745759350, Local endogenous regulators of functional immune plasticity in the periodontium
OpenAlex ID: W3039468532