TY - JOUR
T1 - M2b macrophage polarization accompanied with reduction of long noncoding RNA GAS5
AU - Ito, Ichiaki
AU - Asai, Akira
AU - Suzuki, Sumihiro
AU - Kobayashi, Makiko
AU - Suzuki, Fujio
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/11/4
Y1 - 2017/11/4
N2 - Macrophages (Mϕ) are highly plastic and change their functional phenotypes depending on microenvironmental signals. Recent studies have shown that microRNAs are involved in the polarization of Mϕ. In this study, we demonstrated that the phenotype of M2bMϕ [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 Mϕ were prepared from bone marrow-derived Mϕ (BMDMϕ) after stimulation with IFNγ [M(IFNγ)/M1Mϕ], IL-4 [M(IL-4)/M2aMϕ], LPS and immobilized IgG [M(LPS + IC)/M2bMϕ], and IL-10 [M(IL-10)/M2cMϕ]. BMDMϕ cultured with medium [M(no)/quiescent Mϕ] were used as a control. As compared to Μ(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 M2bMϕ) 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. BMDMϕ overexpressed with GAS5 RNA after GAS5 gene transduction did not polarize to M2bMϕ 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 Mϕ polarization stimulated with LPS and IC in combination.
AB - Macrophages (Mϕ) are highly plastic and change their functional phenotypes depending on microenvironmental signals. Recent studies have shown that microRNAs are involved in the polarization of Mϕ. In this study, we demonstrated that the phenotype of M2bMϕ [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 Mϕ were prepared from bone marrow-derived Mϕ (BMDMϕ) after stimulation with IFNγ [M(IFNγ)/M1Mϕ], IL-4 [M(IL-4)/M2aMϕ], LPS and immobilized IgG [M(LPS + IC)/M2bMϕ], and IL-10 [M(IL-10)/M2cMϕ]. BMDMϕ cultured with medium [M(no)/quiescent Mϕ] were used as a control. As compared to Μ(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 M2bMϕ) 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. BMDMϕ overexpressed with GAS5 RNA after GAS5 gene transduction did not polarize to M2bMϕ 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 Mϕ polarization stimulated with LPS and IC in combination.
KW - Bone marrow-derived macrophages
KW - Long noncoding RNA GAS5
KW - Macrophage polarization
KW - Nonsense-mediated RNA decay
UR - http://www.scopus.com/inward/record.url?scp=85029556958&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.09.053
DO - 10.1016/j.bbrc.2017.09.053
M3 - Article
C2 - 28917839
AN - SCOPUS:85029556958
SN - 0006-291X
VL - 493
SP - 170
EP - 175
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -