{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:45:02Z","timestamp":1789544702624,"version":"build-2803163510"},"reference-count":23,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[2009]]},"abstract":"<i>Background:<\/i> Secretory phospholipases A<sub>2<\/sub> (sPLA<sub>2<\/sub>) are an emerging class of mediators of inflammation. These enzymes are released in vivo in patients with systemic inflammatory diseases and allergic disorders. sPLA<sub>2<\/sub>s may activate inflammatory cells by both enzymatic and nonenzymatic mechanisms. The aim of this study was to evaluate the effect of the inhaled glucocorticoid budesonide on sPLA<sub>2<\/sub>-induced activation of primary human macrophages. <i>Methods:<\/i> Macrophages isolated from human lung tissue were preincubated (3\u201318 h) with budesonide (1\u20131,000 n<i>M<\/i>) before stimulation with 2 distinct sPLA<sub>2<\/sub>s (group IA and group X). At the end of incubation the release of TNF-\u03b1, IL-6 and IL-8 was assessed by ELISA. Specific mRNA for these products was determined by quantitative RT-PCR. Activation of mitogen-activated kinases ERK 1\/2 and p38 was assessed by Western blot. <i>Results:<\/i> Budesonide inhibited the release of TNF-\u03b1, IL-6 and IL-8 from sPLA<sub>2<\/sub>-stimulated macrophages in a concentration-dependent manner. The inhibitory effect of budesonide was due to a reduction of gene expression and was complete after 18 h of preincubation. Budesonide had no effect on sPLA<sub>2<\/sub>-induced arachidonic acid mobilization and exocytosis, assessed as \u03b2-glucuronidase release. Suppression of cytokine\/chemokine production by budesonide was associated with inhibition of sPLA<sub>2<\/sub>-induced ERK 1\/2 and p38 activation. <i>Conclusions:<\/i> Budesonide inhibits the production of proinflammatory cytokines\/chemokines from human lung macrophages activated by sPLA<sub>2<\/sub>. Budesonide represents the first example of a drug able to block the nonenzymatic effects of sPLA<sub>2<\/sub> on human inflammatory cells and, therefore, may provide a useful therapeutic options for diseases associated with enhanced release of sPLA<sub>2<\/sub>s in vivo.<\/jats:p>","DOI":"10.1159\/000218117","type":"journal-article","created":{"date-parts":[[2009,5,11]],"date-time":"2009-05-11T14:20:03Z","timestamp":1242051603000},"page":"144-155","source":"Crossref","is-referenced-by-count":24,"title":["Inhibition of Secretory Phospholipase A<sub>2<\/sub>-Induced Cytokine Production in Human Lung Macrophages by Budesonide"],"prefix":"10.1159","volume":"150","author":[{"given":"Massimo","family":"Triggiani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francescopaolo","family":"Granata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Petraroli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Loffredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annunziata","family":"Frattini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria Ilaria","family":"Staiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Marone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2009,5,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1248%2Fbpb.27.1158"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3109%2F01902149609031777"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016%2FS0954-6111%2896%2990175-4"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2F0954-6111%2895%2990089-6"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1007%2FBF01705721"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1084%2Fjem.183.5.2235"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1042%2FBJ20041307"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1398-9995.2007.01381.x"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2005.08.011"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002%2Feji.200535567"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016%2FS0091-6749%2802%2980002-1"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1006%2Fphrs.2002.0969"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-2952%2897%2900018-X"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2006.09.027"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016%2F0165-5728%2892%2990144-A"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.coph.2004.06.009"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1067%2Fmai.2002.122712"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1034%2Fj.1398-9995.1999.00087.x"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1159%2F000071481"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M906304199"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1093%2Femboj%2F20.24.7108"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1002%2Fjcp.20884"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1081%2FJAS-200044748"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/218117","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/218117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T22:21:21Z","timestamp":1745446881000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000218117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,9,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000218117","archive":["Portico"],"relation":{},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009]]}}}