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Nontypeable <jats:italic>Haemophilus influenzae<\/jats:italic> (NTHi) is a major bacterial pathogen for OM. OM characterized by the presence of overactive inflammatory responses is due to the aberrant production of inflammatory mediators including C-X-C motif chemokine ligand 5 (CXCL5). The molecular mechanism underlying induction of CXCL5 by NTHi is unknown. Here we show that NTHi up-regulates CXCL5 expression by activating IKK\u03b2-I\u03baB\u03b1 and p38 MAPK pathways via NF-\u03baB nuclear translocation-dependent and -independent mechanism in middle ear epithelial cells. Current therapies for OM are ineffective due to the emergence of antibiotic-resistant NTHi strains and risk of side effects with prolonged use of immunosuppressant drugs. In this study, we show that curcumin, derived from <jats:italic>Curcuma longa<\/jats:italic> plant, long known for its medicinal properties, inhibited NTHi-induced CXCL5 expression <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Curcumin suppressed CXCL5 expression by direct inhibition of IKK\u03b2 phosphorylation and inhibition of p38 MAPK via induction of negative regulator MKP-1. Thus, identification of curcumin as a potential therapeutic for treating OM is of particular translational significance due to the attractiveness of targeting overactive inflammation without significant adverse effects.<\/jats:p>","DOI":"10.1038\/srep31695","type":"journal-article","created":{"date-parts":[[2016,8,19]],"date-time":"2016-08-19T11:21:07Z","timestamp":1471605667000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Curcumin suppresses NTHi-induced CXCL5 expression via inhibition of positive IKK\u03b2 pathway and up-regulation of negative MKP-1 pathway"],"prefix":"10.1038","volume":"6","author":[{"given":"Anuhya S.","family":"Konduru","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung-Cheol","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Dong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,8,19]]},"reference":[{"key":"BFsrep31695_CR1","doi-asserted-by":"publisher","first-page":"E52","DOI":"10.1177\/0194599813479772","volume":"148","author":"JD Li","year":"2013","unstructured":"Li, J. 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