{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:15:39Z","timestamp":1789848939355,"version":"4.0.1"},"reference-count":100,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory responses by the innate and adaptive immune systems protect against infections and are essential to health and survival. Many diseases including atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, and obesity involve persistent chronic inflammation. Currently available anti-inflammatory agents, including non-steroidal anti-inflammatory drugs, steroids, and biologics, are often unsafe for chronic use due to adverse effects. The development of effective non-toxic anti-inflammatory agents for chronic use remains an important research arena. We previously reported that oral administration of Oxy210, a semi-synthetic oxysterol, ameliorates non-alcoholic steatohepatitis (NASH) induced by a high-fat diet in APOE*3-Leiden.CETP humanized mouse model of NASH and inhibits expression of hepatic and circulating levels of inflammatory cytokines. Here, we show that Oxy210 also inhibits diet-induced white adipose tissue inflammation in APOE*3-Leiden.CETP mice, evidenced by the inhibition of adipose tissue expression of IL-6, MCP-1, and CD68 macrophage marker. Oxy210 and related analogs exhibit anti-inflammatory effects in macrophages treated with lipopolysaccharide in vitro, mediated through inhibition of toll-like receptor 4 (TLR4), TLR2, and AP-1 signaling, independent of cyclooxygenase enzymes or steroid receptors. The anti-inflammatory effects of Oxy210 are correlated with the inhibition of macrophage polarization. We propose that Oxy210 and its structural analogs may be attractive candidates for future therapeutic development for targeting inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms23105478","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T09:27:56Z","timestamp":1652520476000},"page":"5478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Oxy210, a Semi-Synthetic Oxysterol, Exerts Anti-Inflammatory Effects in Macrophages via Inhibition of Toll-like Receptor (TLR) 4 and TLR2 Signaling and Modulation of Macrophage Polarization"],"prefix":"10.3390","volume":"23","author":[{"given":"Feng","family":"Wang","sequence":"first","affiliation":[{"name":"MAX BioPharma Inc., Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Stappenbeck","sequence":"additional","affiliation":[{"name":"MAX BioPharma Inc., Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu-Ya","family":"Tang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular & Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2753-7601","authenticated-orcid":false,"given":"Ying E.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular & Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldons J.","family":"Lusis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-294X","authenticated-orcid":false,"given":"Farhad","family":"Parhami","sequence":"additional","affiliation":[{"name":"MAX BioPharma Inc., Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cell.2010.02.043","article-title":"Anti-inflammatory agents: Present and future","volume":"140","author":"Dinarello","year":"2010","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2147\/JIR.S278514","article-title":"Overview on the discovery and development of anti-inflammatory drugs: Should the focus be on synthesis or degradation of PGE2?","volume":"14","author":"Mahesh","year":"2021","journal-title":"J. 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