Macrophages (M phi) are highly plastic and change their functional phenotypes depending on microenvironmental signals. Recent studies have shown that microRNAs are involved in the polarization of Mil). In this study, we demonstrated that the phenotype of M2bM phi [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 M phi were prepared from bone marrow-derived M phi (BMDM phi) after stimulation with IFN gamma [M(IFN gamma)/M1M phi], IL-4 [M(IL-4)/M2aM phi], LPS and immobilized IgG [M(LPS + IC)/ M2bM phi], and IL -10 [M(IL-10)/M2cM phi]. BMDM phi cultured with medium [M(no)/quiescent M phi] were used as a control. As compared to M(no), M(IFNy), 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 M2bM phi) 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. BMDM phi overexpressed with GAS5 RNA after GAS5 gene transduction did not polarize to M2bM phi 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 M phi polarization stimulated with LPS and IC in combination. (C) 2017 Elsevier Inc. All rights reserved.