| First Author | Zhu D | Year | 2013 |
| Journal | J Allergy Clin Immunol | Volume | 132 |
| Issue | 2 | Pages | 426-36.e8 |
| PubMed ID | 23562609 | Mgi Jnum | J:263378 |
| Mgi Id | MGI:6189251 | Doi | 10.1016/j.jaci.2013.02.005 |
| Citation | Zhu D, et al. (2013) MicroRNA-17/20a/106a modulate macrophage inflammatory responses through targeting signal-regulatory protein alpha. J Allergy Clin Immunol 132(2):426-36.e8 |
| abstractText | BACKGROUND: Signal-regulatory protein alpha (SIRPalpha) is an essential signaling molecule that modulates leukocyte inflammatory responses. However, the regulation of selective SIRPalpha synthesis and its dynamic changes in leukocytes under inflammatory stimulation remain incompletely understood. OBJECTIVE: We sought to identify the microRNAs (miRNAs) that posttranscriptionally regulate SIRPalpha synthesis and their roles in modulating macrophage inflammatory responses. METHODS: SIRPalpha was induced in SIRPalpha-negative promyelocytic cells by retinoic acid or phorbol 12-myristate 13-acetate, and the differential expression of miRNAs was assessed by means of microarray and quantitative RT-PCR assays. The roles of identified miRNAs in controlling SIRPalpha synthesis in leukocytes and leukocyte inflammatory responses were determined. RESULTS: We identified SIRPalpha as a common target gene of miR-17, miR-20a, and miR-106a. During SIRPalpha induction, levels of these 3 miRNAs were all reduced, and their downregulation by retinoic acid or phorbol 12-myristate 13-acetate occurred through suppression of the c-Myc signaling pathway. All miR-17, miR-20a, and miR-106a specifically bound to the same seed sequence within the SIRPalpha 3' untranslated region and correlated inversely with SIRPalpha protein levels in various cells. In macrophages upregulation of miR-17, miR-20a, and miR-106a by LPS served as the mechanism underlying LPS-induced SIRPalpha reduction and macrophage activation. Both in vitro and in vivo assays demonstrate that miR-17, miR-20a, and miR-106a regulate macrophage infiltration, phagocytosis, and proinflammatory cytokine secretion through targeting SIRPalpha. CONCLUSION: These findings demonstrate for the first time that miR-17, miR-20a, and miR-106a regulate SIRPalpha synthesis and SIRPalpha-mediated macrophage inflammatory responses in a redundant fashion, providing a novel pathway in which a panel of miRNAs can modulate immune polarization through regulation of macrophage activation. |
