MicroRNA-155 is induced during the macrophage inflammatory response.
The mammalian inflammatory response to infection involves the induction of several hundred genes, a process that must be carefully regulated to achieve pathogen clearance and prevent the consequences of unregulated expression, such as cancer. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators that has also been linked to cancer. However, the relationship between inflammation, innate immunity, and miRNA expression is just beginning to be explored. In the present study, we use microarray technology to identify miRNAs induced in primary murine macrophages after exposure to polyriboinosinic:polyribocytidylic acid or the cytokine IFN-beta. miR-155 was the only miRNA of those tested that was substantially up-regulated by both stimuli. It also was induced by several Toll-like receptor ligands through myeloid differentiation factor 88- or TRIF-dependent pathways, whereas up-regulation by IFNs was shown to involve TNF-alpha autocrine signaling. Pharmacological inhibition of the kinase JNK blocked induction of miR-155 in response to either polyriboinosinic:polyribocytidylic acid or TNF-alpha, suggesting that miR-155-inducing signals use the JNK pathway. Together, these findings characterize miR-155 as a common target of a broad range of inflammatory mediators. Importantly, because miR-155 is known to function as an oncogene, these observations identify a potential link between inflammation and cancer.
O'Connell
Ryan M
RM
Department of Biology, California Institute of Technology, 330 Braun, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Taganov
Konstantin D
KD
Boldin
Mark P
MP
Cheng
Genhong
G
Baltimore
David
D
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D007249:Inflammation; D016899:Interferon-beta / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D015854:Up-Regulation
D035683:MicroRNAs; D016899:Interferon-beta; D011070:Poly I-C