{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:18:56Z","timestamp":1778656736046,"version":"3.51.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>LPS and IFN-\u03b3 alone or in combination have been implicated in the development of steroid resistance. Combined LPS\/IFN-\u03b3 strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS\/IFN-\u03b3\u2013induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes\/macrophages, and BALB\/c mice were treated with LPS\/IFN-\u03b3, in the presence and absence of dexamethasone and\/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS\/IFN-\u03b3\u2013induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS\/IFN-\u03b3\u2013induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes\/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS\/IFN-\u03b3 markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS\/IFN-\u03b3 also decreased total HDAC activity but increased the total histone acetyltransferase\/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase\/HDAC activity ratio in mouse lungs exposed to LPS\/IFN-\u03b3, possibly via suppression of PI3K\/Akt\/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2\u2013related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders such as asthma.<\/jats:p>","DOI":"10.4049\/jimmunol.1502114","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T01:59:02Z","timestamp":1462240742000},"page":"4706-4712","source":"Crossref","is-referenced-by-count":28,"title":["Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide\/IFN-\u03b3\u2013Induced IL-27 and Airway Hyperresponsiveness in Mice"],"prefix":"10.1093","volume":"196","author":[{"given":"Wupeng","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , Singapore 117600"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-5698","authenticated-orcid":false,"given":"W S Daniel","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , Singapore 117600"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W S Fred","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , Singapore 117600"},{"name":"Immunology Program, Life Science Institute, National University of Singapore , Singapore 117456"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,6,1]]},"reference":[{"key":"2025030702174498300_r1","doi-asserted-by":"crossref","first-page":"e47971","DOI":"10.1371\/journal.pone.0047971","article-title":"Alveolar macrophages play a key role in cockroach-induced allergic inflammation via TNF-\u03b1 pathway","volume":"7","author":"Kim","year":"2012","journal-title":"PLoS One"},{"key":"2025030702174498300_r2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.jaci.2014.04.020","article-title":"Neonatal rhinovirus induces mucous metaplasia and airways hyperresponsiveness through IL-25 and type 2 innate lymphoid cells","volume":"134","author":"Hong","year":"2014","journal-title":"J. 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