%0 Journal Article
%T Expression profiling in vivo demonstrates rapid changes in lung microRNA levels following lipopolysaccharide-induced inflammation but not in the anti-inflammatory action of glucocorticoids
%A Sterghios A Moschos
%A Andrew E Williams
%A Mark M Perry
%A Mark A Birrell
%A Maria G Belvisi
%A Mark A Lindsay
%J BMC Genomics
%D 2007
%I BioMed Central
%R 10.1186/1471-2164-8-240
%X To address this question, we have examined the differential expression of 104 miRNAs using real-time PCR during the innate immune response in mouse lung following exposure to aerosilised lipopolysaccharide (LPS). Following challenge, we observed rapid and transient increase in both the mean (4.3-fold) and individual levels of miRNA expression (46 miRNAs) which peaked at 3 hrs. Crucially, this increase was correlated with a reduction in the expression of tumour necrosis factor (TNF)-¦Á, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2, suggesting a potential role for miRNAs in the regulation of inflammatory cytokine production. Examination of the individual miRNA expression profiles showed time dependent increases in miR-21, -25, -27b, -100, 140, -142-3p, -181c, 187, -194, -214, -223 and -224. Corticosteroid studies showed that pre-treatment with dexamethasone at concentrations that inhibited TNF-¦Á production, had no effect either alone or upon the LPS-induced miRNA expression profile.We have shown that the LPS-induced innate immune response is associated with widespread, rapid and transient increases in miRNA expression in the mouse lung and we speculate that these changes might be involved in the regulation of the inflammatory response. In contrast, the lack of effect of dexamethasone in either control or challenged animals implies that the actions of glucocorticoids per se are not mediated through changes in miRNAs expression and that LPS-induced increases in miRNA expression are not mediated via classical inflammatory transcription factors.RNA interference (RNAi), mediated by 19- to 23- nucleotide double stranded RNA, has been identified as an evolutionarily conserved mechanism for the post-transcriptional regulation of mammalian gene expression [1]. Initial studies implicated RNAi in the cellular response to viral infection following the demonstration that virally-derived double stranded RNA was cleaved by the action of the RNase-II
%U http://www.biomedcentral.com/1471-2164/8/240