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At present, type III IFN genes are the least well-characterized IFN types. Here, we demonstrate that the p38 MAPK signaling pathway is involved in regulating IFN-\u03bb1 gene expression in response to various types of RNA molecules in human moDCs. Inhibition of p38 MAPK strongly reduced IFN gene expression, and overexpression of p38\u03b1 MAPK enhanced IFN-\u03bb1 gene expression in RNA-stimulated moDCs. The regulation of IFN gene expression by p38 MAPK signaling was independent of protein synthesis and thus, a direct result of RNA stimulation. Moreover, the RIG-I\/MDA5-MAVS-IRF3 pathway was required for p38\u03b1 MAPK to up-regulate IFN-\u03bb1 promoter activation, whereas the MyD88-IRF7 pathway was not needed, and the regulation was not involved directly in IRF7-dependent IFN-\u03b11 gene expression. The stimulatory effect of p38\u03b1 MAPK on IFN-\u03bb1 mRNA expression in human moDCs did not take place directly via the activating TBK1\/IKK\u025b complex, but rather, it occurred through some other parallel pathways. Furthermore, mutations in ISRE and NF-\u03baB binding sites in the promoter region of the IFN-\u03bb1 gene led to a significant reduction in p38\u03b1 MAPK-mediated IFN responses after RNA stimulation. Altogether, our data suggest that the p38\u03b1 MAPK pathway is linked with RLR signaling pathways and regulates the expression of early IFN genes after RNA stimulation cooperatively with IRF3 and NF-\u03baB to induce antiviral responses further.<\/jats:p>","DOI":"10.1189\/jlb.2a0114-059rr","type":"journal-article","created":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T02:10:22Z","timestamp":1417659022000},"page":"307-320","source":"Crossref","is-referenced-by-count":25,"title":["MAP kinase p38<i>\u03b1<\/i> regulates type III interferon (<i>IFN-<\/i>\u03bb<i>1<\/i>) gene expression in human monocyte-derived dendritic cells in response to RNA stimulation"],"prefix":"10.1093","volume":"97","author":[{"given":"Miao","family":"Jiang","sequence":"first","affiliation":[{"name":"Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare , Helsinki , Finland"},{"name":"Institute of Biotechnology, University of Helsinki , Finland"},{"name":"Department of Biosciences, University of Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"O\u00a8sterlund","sequence":"additional","affiliation":[{"name":"Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare , Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riku","family":"Fagerlund","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California , San Diego, La Jolla, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana N","family":"Rios","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California , San Diego, La Jolla, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California , San Diego, La Jolla, California , USA"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, Institute for Quantitative and Computational Biosciences, University of California , Los Angeles, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna M","family":"Poranen","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis H","family":"Bamford","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, University of Helsinki , Finland"},{"name":"Department of Biosciences, University of Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Julkunen","sequence":"additional","affiliation":[{"name":"Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare , Helsinki , Finland"},{"name":"Department of Virology, University of Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,12,3]]},"reference":[{"key":"2023013012465346500_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/SQB.1989.054.01.003","article-title":"Approaching the asymptote? 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