{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:05:49Z","timestamp":1772118349527,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T00:00:00Z","timestamp":1318896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Statins are prescribed to 25 million people worldwide for treating hypercholesterolemia and reducing the risk of cardiovascular diseases. However, the side effects of statins on immunity, and particularly on DC immunobiology, have not been analyzed in\u2010depth. Here, we have investigated the impact of lovastatin treatment during monocyte differentiation into DCs on the responsiveness of the resulting monocyte\u2010derived DCs (moDCs) to TLR\u2010mediated activation. Lovastatin positively regulated TLR4 signaling in LPS\u2010stimulated moDCs, leading to strong activation of p38 MAP\u2010kinase paralleled by increased proinflammatory cytokine and IFN\u2010\u03b2 production. In contrast, lovastatin promoted negative regulation of IFN\u2010\u03b2\u2010mediated autocrine signaling through the IFN\u2010\u03b1\u03b2 receptor, paralleled by low expression of the transcription factor IRF\u20101, leading to the inhibition of the enzymes iNOS and HO\u20101. Defective activation of iNOS\/HO\u20101 resulted in limited cytoprotective capacity against ROS and reduced microbicidal potential. These data were validated using an in vivo model of\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    infection, which revealed that iNOS activation by splenic inflammatory moDCs, specialized in NO and TNF\u2010\u03b1 production, was strongly reduced in lovastatin\u2010treated,\n                    <jats:italic>Listeria<\/jats:italic>\n                    \u2010infected mice. Statin treatment could have severe implications in immunity against pathogens due to defective iNOS\/HO\u20101 metabolism activation in inflammatory moDCs that might lead to immune failure.\n                  <\/jats:p>","DOI":"10.1002\/eji.201141674","type":"journal-article","created":{"date-parts":[[2011,8,31]],"date-time":"2011-08-31T16:44:19Z","timestamp":1314809059000},"page":"3330-3339","source":"Crossref","is-referenced-by-count":13,"title":["Statins inhibit iNOS\u2010mediated microbicidal potential of activated monocyte\u2010derived dendritic cells by an IFN\u2010\u03b2\u2010dependent mechanism"],"prefix":"10.1002","volume":"41","author":[{"given":"Pilar M.","family":"Dom\u00ednguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"L\u00f3pez\u2010Bravo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Ardav\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,18]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.2.207"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.043"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-8749(03)00148-5"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0205064"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636567"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00876.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808664200"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00393-7"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1839"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.12.004"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001-907"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00171-7"},{"key":"e_1_2_6_15_2","first-page":"1","article-title":"iNOS\u2010producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL\/6 resistant mice","volume":"6","author":"De Trez C.","year":"2009","journal-title":"PLoS Pathog."},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.1107"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.69.4.598"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00181-9"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.1674"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08476"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.12.7377"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.091301.131133"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.65.070196.001325"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838189"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.08.044"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119812"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1461"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0286"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201141674","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201141674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T11:20:52Z","timestamp":1697455252000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201141674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,18]]},"references-count":27,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.1002\/eji.201141674"],"URL":"https:\/\/doi.org\/10.1002\/eji.201141674","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13485015.14862140","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,18]]}}}