miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection

Moon, Hyung‐Geun; Yang, Jincheng; Zheng, Yijie; Jin, Yang

doi:10.4049/jimmunol.1401372

Cited by 74 publications

(65 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support of these findings, miR15a overexpressing mice had decreased levels of Foxo1, NLRP3, cleaved caspase 1, and IL-1β levels. Work in myeloid cells where miR15a was deleted showed increased phagocytic and bactericidal capability of bone marrow-derived macrophages through an upregulation of TLR4 (Moon et al, 2014), which is in agreement with our findings. TLR4 has been shown to prime the NLRP3 inflammasome in high-fat derived dendritic cells compared to chow-derived cells, leading to increased sensitivity to inflammatory stimuli (Reynolds et al, 2012).…”

Section: Discussionsupporting

confidence: 92%

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

Curtiss

Liu

Steinle

2018

Experimental Eye Research

View full text Add to dashboard Cite

We have previously published that miR15a can reduce inflammatory cytokines, which could be key to diabetic retinal pathology. In this work, we wanted to investigate whether miR15a altered NLR pyrin domain 3 (NLRP3) proteins. Whole retinal lysates from both miR15a overexpressing mice and endothelial cell specific miR15a/16 knockout mice were used to investigate protein levels of forkhead box protein O1 (Foxo1), NLRP3, cleaved caspase 1 and interleukin-1 beta (IL-1β). Primary human retinal endothelial cells (REC) were cultured in normal and high glucose followed by transfection with a miR15a mimic for protein analyses. MiR15a expression was verified by quantitative PCR, and a luciferase binding assay was used to examine whether miR15a directly bound Foxo1. In mouse retinal lysates, loss of miR15a increased Foxo1, IL-1β, NLRP3, and cleaved caspase 1 levels. REC grown in high glucose transfected with the miR15a mimic had decreased levels of Foxo1 and NLRP3. miR15a directly binds to Foxo1. miR15a regulates NLRP3 actions in the retinal vasculature. Work in mice showed that loss of miR15a increased NLRP3 pathway signaling and Foxo1. miR15a mimics decreased levels of Foxo1 and NLRP3. Taken together, miR15a reduced inflammasome proteins and Foxo1 levels in the retinal vasculature.

show abstract

Section: Discussionsupporting

confidence: 92%

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

Curtiss

Liu

Steinle

2018

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…miR-15a/16 has been shown to regulate macrophage phagocytosis after bacterial infection (49). miR-21 has also been shown to play a role in the process of engulfment of apoptotic cells by macrophages (56).…”

Section: Discussionmentioning

confidence: 99%

“…miR-27a Mediates the Process of Phagocytosis by Regulating CD206 Expression-miRNAs have emerged as regulators of phagocytosis in myeloid cells (48,49). Thus, we wanted to evaluate the role of miR-27a in increased phagocytosis induced by alcohol EVs.…”

Section: Mir-27a-loaded Evs Have Functional Effects On Naivementioning

confidence: 99%

MicroRNA Cargo of Extracellular Vesicles from Alcohol-exposed Monocytes Signals Naive Monocytes to Differentiate into M2 Macrophages

Saha¹,

Momen-Heravi²,

Kodys

et al. 2016

Journal of Biological Chemistry

194

155

View full text Add to dashboard Cite

Membrane-coated extracellular vesicles (EVs) released by cells can serve as vehicles for delivery of biological materials and signals.Recently, we demonstrated that alcohol-treated hepatocytes cross-talk with immune cells via exosomes containing microRNA (miRNAs). Here, we hypothesized that alcohol-exposed monocytes can communicate with naive monocytes via EVs. We observed increased numbers of EVs, mostly exosomes, secreted by primary human monocytes and THP-1 monocytic cells in the presence of alcohol in a concentration-and time-dependent manner. EVs derived from alcohol-treated monocytes stimulated naive monocytes to polarize into M2 macrophages as indicated by increased surface expression of CD68 (macrophage marker), M2 markers (CD206 (mannose receptor) and CD163 (scavenger receptor)), secretion of IL-10, and TGF␤ and increased phagocytic activity. miRNA profiling of the EVs derived from alcohol-treated THP-1 monocytes revealed high expression of the M2-polarizing miRNA, miR-27a. Treatment of naive monocytes with control EVs overexpressing miR-27a reproduced the effect of EVs from alcohol-treated monocytes on naive monocytes and induced M2 polarization, suggesting that the effect of alcohol EVs was mediated by miR-27a. We found that miR27a modulated the process of phagocytosis by targeting CD206 expression on monocytes. Importantly, analysis of circulating EVs from plasma of alcoholic hepatitis patients revealed increased numbers of EVs that contained high levels of miR-27a as compared with healthy controls. Our results demonstrate the following: first, alcohol increases EV production in monocytes; second, alcoholexposed monocytes communicate with naive monocytes via EVs; and third, miR-27a cargo in monocyte-derived EVs can program naive monocytes to polarize into M2 macrophages.

show abstract

“…Exposure of cell lines and animal models to LPS is a popular method for investigating their roles in inflammation. In an LPS model of murine sepsis, an increased expression of miR-15a/16 reduced the phagocytic activity of macrophages and increased mitochondrial oxidative stress, resulting in a proinflammatory phenotype [59, 60]. Overexpression of miR-15a/16 in the LPS-treated murine macrophage RAW264.7 downregulated the expression of Toll-like receptor (TLR)4 and IL-1 receptor-associated kinase 1 (IRAK1), contributing to immunosuppressive phenotypes [53, 61].…”

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

View full text Add to dashboard Cite

BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

show abstract

miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection

Cited by 74 publications

References 49 publications

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

MicroRNA Cargo of Extracellular Vesicles from Alcohol-exposed Monocytes Signals Naive Monocytes to Differentiate into M2 Macrophages

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Contact Info

Product

Resources

About