Microregulating Inflammatory Responses

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Science  16 Feb 2007:
Vol. 315, Issue 5814, pp. 915
DOI: 10.1126/science.315.5814.915c

Inflammatory responses help protect against infection, but these signaling pathways may also contribute to some diseases. O'Connell et al. have investigated the fate of microRNAs (miRNAs) during viral infection. They monitored the expression of 200 miRNAs in response to polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA that is used to mimic viral infection, or to the antiviral cytokine interferon-β (IFN-β). One such miRNA, miR-155, showed increased expression in macrophages in response to both stimuli. The response to poly(I:C) required upstream signaling via Toll receptors and the MyD88 or TRIF adaptor proteins. Interferons, on the other hand, stimulated expression of miR-155 through a slower pathway that required autocrine signals mediated by tumor necrosis factor-α. The two pathways were shown to converge onto the JNK mitogen-activated protein kinase as a JNK inhibitor blocked both miR-155 responses. Because the gene encoding miR-155 is a site where avian retroviruses integrate, and miR-155 over-expression can cause B cell lymphoma in mice, the finding of miR-155 as a target of pathways activated by viral infection presents a link between inflammatory responses and cancer. — LBR

Proc. Natl. Acad. Sci. U.S.A. 104, 1604 (2007).

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