Author:
Moschos Sterghios A,Williams Andrew E,Perry Mark M,Birrell Mark A,Belvisi Maria G,Lindsay Mark A
Abstract
Abstract
Background
At present, nothing is known of the role of miRNAs in the immune response in vivo despite the fact that inflammation is thought to underlie multiple acute and chronic diseases. In these circumstances, patients are commonly treated with corticosteroids such as dexamethasone.
Results
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)-α, 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-α production, had no effect either alone or upon the LPS-induced miRNA expression profile.
Conclusion
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.
Publisher
Springer Science and Business Media LLC
Cited by
248 articles.
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