TY - JOUR
T1 - Macrophage-derived apoptotic bodies promote the proliferation of the recipient cells via shuttling microRNA-221/222
AU - Zhu, Ziwen
AU - Zhang, Duo
AU - Lee, Heedoo
AU - Menon, Aravind Ajakumar
AU - Wu, Jingxuan
AU - Hu, Kebin
AU - Jin, Yang
N1 - Funding Information:
This work is support by the U.S. National Institutes of Health Grants R01 HL102076, R21 AI121644, and R01 GM111313 (all to Y.J.).
Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2017
Y1 - 2017
N2 - Bacterial pneumonia is a common and serious clinical entity. Alveolar epithelial cells and alveolar macrophages are the first line of defense in the innate immunity against bacterial pathogens. Epithelial cells are known to release chemokines/cytokines that recruit and activate phagocytic cells. However, the signals sent from alveolar macrophages back to the lung epithelial cells remain largely unexplored. We found that LPS, a wellrecognized stimulator derived from gram-negative (G-) bacteria, rapidly and robustly induces the secretion of macrophage-derived extracellular vesicles (EVs). The main type of EVs found in the early stages after LPS stimulation are apoptotic bodies (ABs) and not microvesicles (MVs) or exosomes (Exos). Furthermore, LPS markedly up-regulate the levels of a repertoire of microRNAs (miRNAs) in the macrophage-derived ABs, including miR-221 and miR-222. Functionally, the LPSinduced, macrophage-derived ABs promote the proliferation of malignant and/or normal lung epithelial cells. We next directly transfected miR-221 and/or miR-222 inhibitors into the LPS-induced ABs. Deletion of miR-221/ 222 in ABs significantly reduces the AB-mediated proliferation of lung epithelial cells. Mechanistically, AB-shuttling miR-221/222 promote cell growth by modulating cyclin-dependent kinase inhibitor 1B (CDKN1B) pathways. Collectively, LPS-induced, macrophagederived ABs promote the proliferation of their recipient epithelial cells, partially via AB-shuttling miRNAs.
AB - Bacterial pneumonia is a common and serious clinical entity. Alveolar epithelial cells and alveolar macrophages are the first line of defense in the innate immunity against bacterial pathogens. Epithelial cells are known to release chemokines/cytokines that recruit and activate phagocytic cells. However, the signals sent from alveolar macrophages back to the lung epithelial cells remain largely unexplored. We found that LPS, a wellrecognized stimulator derived from gram-negative (G-) bacteria, rapidly and robustly induces the secretion of macrophage-derived extracellular vesicles (EVs). The main type of EVs found in the early stages after LPS stimulation are apoptotic bodies (ABs) and not microvesicles (MVs) or exosomes (Exos). Furthermore, LPS markedly up-regulate the levels of a repertoire of microRNAs (miRNAs) in the macrophage-derived ABs, including miR-221 and miR-222. Functionally, the LPSinduced, macrophage-derived ABs promote the proliferation of malignant and/or normal lung epithelial cells. We next directly transfected miR-221 and/or miR-222 inhibitors into the LPS-induced ABs. Deletion of miR-221/ 222 in ABs significantly reduces the AB-mediated proliferation of lung epithelial cells. Mechanistically, AB-shuttling miR-221/222 promote cell growth by modulating cyclin-dependent kinase inhibitor 1B (CDKN1B) pathways. Collectively, LPS-induced, macrophagederived ABs promote the proliferation of their recipient epithelial cells, partially via AB-shuttling miRNAs.
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U2 - 10.1189/jlb.3A1116-483R
DO - 10.1189/jlb.3A1116-483R
M3 - Article
C2 - 28274991
AN - SCOPUS:85020198209
SN - 0741-5400
VL - 101
SP - 1349
EP - 1359
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -