Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5504621 | Biochemical and Biophysical Research Communications | 2017 | 6 Pages |
Abstract
Macrophages (MÏ) are highly plastic and change their functional phenotypes depending on microenvironmental signals. Recent studies have shown that microRNAs are involved in the polarization of MÏ. In this study, we demonstrated that the phenotype of M2bMÏ [CCL1(+) IL-10(+) LIGHT(+)] switches to other phenotypes with interchangeability attained through the increased expression of growth arrest-specific 5 RNA (GAS5 RNA), a long noncoding RNA. GAS5 RNA has been described as a silencer of the CCL1 gene. Various phenotypes of MÏ were prepared from bone marrow-derived MÏ (BMDMÏ) after stimulation with IFNγ [M(IFNγ)/M1MÏ], IL-4 [M(IL-4)/M2aMÏ], LPS and immobilized IgG [M(LPS + IC)/M2bMÏ], and IL-10 [M(IL-10)/M2cMÏ]. BMDMÏ cultured with medium [M(no)/quiescent MÏ] were used as a control. As compared to Î(no), M(IFNγ), M(IL-4) and M(IL-10), the reduced level of GAS5 RNA was shown in M(LPS + IC). CCL1 and LIGHT mRNAs (typical biomarkers of M2bMÏ) were not expressed by M(LPS + IC) transduced with a GAS5 gene using lentiviral vector. The reduction of GAS5 RNA in M(LPS + IC) was mediated by the activation of nonsense-mediated RNA decay (NMD) pathway. BMDMÏ overexpressed with GAS5 RNA after GAS5 gene transduction did not polarize to M2bMÏ even though they were stimulated with LPS and IC in combination. These results indicate that the reduction of GAS5 RNA influenced by the NMD pathway activation leads to the MÏ polarization stimulated with LPS and IC in combination.
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Authors
Ichiaki Ito, Akira Asai, Sumihiro Suzuki, Makiko Kobayashi, Fujio Suzuki,