Abstract:
BACKGROUND:Secretory phospholipases A(2) (sPLA(2)) are an emerging class of mediators of inflammation. These enzymes are released in vivo in patients with systemic inflammatory diseases and allergic disorders. sPLA(2)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(2)-induced activation of primary human macrophages. METHODS:Macrophages isolated from human lung tissue were preincubated (3-18 h) with budesonide (1-1,000 nM) before stimulation with 2 distinct sPLA(2)s (group IA and group X). At the end of incubation the release of TNF-alpha, 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. RESULTS:Budesonide inhibited the release of TNF-alpha, IL-6 and IL-8 from sPLA(2)-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(2)-induced arachidonic acid mobilization and exocytosis, assessed as beta-glucuronidase release. Suppression of cytokine/chemokine production by budesonide was associated with inhibition of sPLA(2)-induced ERK 1/2 and p38 activation. CONCLUSIONS:Budesonide inhibits the production of proinflammatory cytokines/chemokines from human lung macrophages activated by sPLA(2). Budesonide represents the first example of a drug able to block the nonenzymatic effects of sPLA(2) on human inflammatory cells and, therefore, may provide a useful therapeutic options for diseases associated with enhanced release of sPLA(2)s in vivo.
journal_name
Int Arch Allergy Immunoljournal_title
International archives of allergy and immunologyauthors
Triggiani M,Granata F,Petraroli A,Loffredo S,Frattini A,Staiano RI,Monaco G,Marone Gdoi
10.1159/000218117subject
Has Abstractpub_date
2009-01-01 00:00:00pages
144-55issue
2eissn
1018-2438issn
1423-0097pii
000218117journal_volume
150pub_type
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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doi:10.1159/000361023
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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doi:10.1159/000236113
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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journal_title:International archives of allergy and immunology
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doi:10.1159/000236884
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doi:10.1159/000237426
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236863
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journal_title:International archives of allergy and immunology
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pub_type: 杂志文章
doi:10.1159/000236406
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章,评审
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236137
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章,评审
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更新日期:2014-01-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000053798
更新日期:2001-05-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237441
更新日期:1997-02-01 00:00:00