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We investigated crosstalk between p38 MAPK inhibitors and corticosteroids in bronchial epithelial cells to investigate synergistic effects on cytokine production and the molecular mechanisms involved. Effects of the p38 MAPK inhibitor BIRB-796 and dexamethasone alone and in combination on LPS, polyI:C or TNF\u03b1 -induced IL-6, CXCL8 and RANTES were assessed in 16HBEs (human epithelial cell line) and on TNF\u03b1-induced IL-6 and CXCL8 in primary human epithelial cells from asthma patients and healthy controls. 16HBEs were used to assess effects of BIRB-796 alone and in combination with dexamethasone on glucocorticoid receptor (GR) activity by reporter gene assay, expression of GR target genes and nuclear localisation using Western blot. The effects of BIRB-796 on TNF\u03b1 stimulated phosphorylation of p38 MAPK and GR at serine (S) 226 by Western blot. Epithelial levels of phosphorylated p38 MAPK and GR S226 were determined by immunohistochemistry in bronchial biopsies from asthma patients and healthy controls. BIRB-796 in combination with dexamethasone increased inhibition of cytokine production in a synergistic manner. Combination treatment significantly increased GR nuclear localisation compared to dexamethasone alone. BIRB-796 inhibited TNF\u03b1-induced p38 MAPK and GR S226 phosphorylation. Phosphorylated GR S226 and p38 MAPK levels were increased in bronchial epithelium of more severe asthma patients. Molecular crosstalk exists between p38 MAPK activation and GR function in human bronchial epithelial cells, which alters GR activity. Combining a p38 MAPK inhibitor and a corticosteroid may demonstrate therapeutic potential in severe asthma<jats:bold>.<\/jats:bold><\/jats:p><\/jats:sec><jats:sec><jats:title>Key messages<\/jats:title><jats:p>\u2022 Combination of corticosteroid and p38 inhibitor in human bronchial epithelial cells<\/jats:p><jats:p>\u2022 Combination increased cytokine inhibition synergistically and nuclear GR<\/jats:p><jats:p>\u2022 p38 MAPK inhibition reduced TNF\u03b1-induced phosphorylation of GR at S226 but not S211<\/jats:p><jats:p>\u2022 Phosphorylated GRS226 and p38 is increased in bronchial epithelium in severe asthma<\/jats:p><jats:p>\u2022 Combining a p38 inhibitor and a corticosteroid may be effective in asthma treatment<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00109-020-01873-3","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T23:02:29Z","timestamp":1579820549000},"page":"361-374","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["P38 MAPK and glucocorticoid receptor crosstalk in bronchial epithelial cells"],"prefix":"10.1007","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-1886","authenticated-orcid":false,"given":"Simon","family":"Lea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Plumb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Gaffey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie","family":"Gaskell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Harbron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"1873_CR1","doi-asserted-by":"publisher","first-page":"14009","DOI":"10.1038\/npjpcrm.2014.9","volume":"24","author":"D Price","year":"2014","unstructured":"Price D, Fletcher M, van der Molen T (2014) Asthma control and management in 8,000 European patients: the REcognise asthma and LInk to symptoms and experience (REALISE) survey. 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