miR-221-3p Drives the Shift of M2-Macrophages to a Pro-Inflammatory Function by Suppressing JAK3/STAT3 Activation

Quero, Lilian; Tiaden, André N.; Hanser, Edveena; Roux, Julien; Łaski, Artur; Hall, Jonathan; Kyburz, Diego

doi:10.3389/fimmu.2019.03087

Cited by 100 publications

(64 citation statements)

References 75 publications

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“…Mir-155 directly targets E2F2, which induces miR-221 expression and down-regulates cyclin-dependent kinases, thereby regulating cell proliferation (32,33). Interestingly, an inversed correlation between miR-155 and miR-221 was recently reported in TLR4-stimulated M1 and M2 macrophages (34). In this settings, high levels of miR-221 shifted M2 macrophages toward a pro-inflammatory M1 phenotype by targeting directly JAK3 and downstream pSTAT3 activation and IL10 secretion.…”

Section: Discussionmentioning

confidence: 90%

miR-155 Contributes to the Immunoregulatory Function of Human Mesenchymal Stem Cells

et al. 2021

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ObjectivesMesenchymal stem/stromal cells (MSCs) are widely investigated in regenerative medicine thanks to their immunomodulatory properties. They exert their anti-inflammatory function thanks to the secretion of a number of mediators, including proteins and miRNAs, which can be released in the extracellular environment or in the cargo of extracellular vesicles (EVs). However, the role of miRNAs in the suppressive function of MSCs is controversial. The aim of the study was to identify miRNAs that contribute to the immunomodulatory function of human bone marrow-derived MSCs (BM-MSCs).MethodsHuman BM-MSCs were primed by coculture with activated peripheral blood mononuclear cells (aPBMCs). High throughput miRNA transcriptomic analysis was performed using Human MicroRNA TaqMan® Array Cards. The immunosuppressive function of miRNAs was investigated in mixed lymphocyte reactions and the delayed type hypersensitivity (DTH) murine model.ResultsUpon priming, 21 out of 377 tested miRNAs were significantly modulated in primed MSCs. We validated the up-regulation of miR-29a, miR-146a, miR-155 and the down-regulation of miR-149, miR-221 and miR-361 in additional samples of primed MSCs. We showed that miR-155 significantly reduced the proliferation of aPBMCs in vitro and inflammation in vivo, using the DTH model. Analysis of miRNA-mRNA interactions revealed miR-221 as a potential target gene that is down-regulated by miR-155 both in primed MSCs and in aPBMCs.ConclusionHere, we present evidence that miR-155 participates to the immunosuppressive function of human BM-MSCs and down-regulates the expression of miR-221 as a possible inflammatory mediator.

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Section: Discussionmentioning

confidence: 90%

miR-155 Contributes to the Immunoregulatory Function of Human Mesenchymal Stem Cells

et al. 2021

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“…This miR was remarkably positively correlated with IL-6 and TNF-α, suggesting that it may be associated with inflammatory responses related to IL-6 and TNF-α in PSD. This miR activated the proinflammatory function of M2-macrophages by regulating JAK3-STAT3 signaling pathway, thus regulating the release of IL-6 and other inflammatory cytokines (28). It could affect the apoptosis of osteoarthritis synovial cells via affecting the secretion level of TNF-α (29).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Values of miR-221-3p in Serum and Cerebrospinal Fluid for Post-Stroke Depression and Analysis of Risk Factors

Cui

Fan-ying

et al. 2021

ijph

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Background: We aimed to explore the diagnostic values of miR-221-3p in serum and cerebrospinal fluid (CSF) for post-stroke depression (PSD) and to analyze the risk factors of the disease. Methods: Admitted to the Second Affiliated Hospital of Harbin Medical University, Harbin, China from May 2013 to May 2020, 136 stroke patients were enrolled, among which 76 PSD patients were taken as a PSD group and 60 non-depressed patients were taken as a Non-PSD group. miR-221-3p expression in serum and CSF and concentrations of inflammatory cytokines (IL-6, TNF-α) in serum were detected, to analyze the diagnostic and prognostic values of the indicators for PSD. Correlations of miR-221-3p in serum with that in CSF, with the National Institute of Health Stroke Scale (NIHSS) score and the Hamilton Depression Rating Scale (HAMD) score, and with inflammatory cytokines were analyzed, so as to analyze the risk factors affecting the occurrence of PSD. Results: Compared with the Non-PSD group, miR-221-3p remarkably upregulated in serum and CSF in the PSD group, and its areas under the curves (AUCs) for PSD identification were 0.900 and 0.925, respectively. According to the correlation analysis, miR-221-3p in serum was remarkably positively correlated with that in CSF, NIHSS score, HAMD score, IL-6 and TNF-α. In addition, a history of mental illness, NIHSS score, HAMD score, IL-6, TNF-α and miR-221-3p were risk factors of PSD. Conclusion: miR-221-3p in serum and CSF can be used as the diagnostic and risk warning indicators of PSD.

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“…MiR-146b and miR-221 seem to have an opposite role of miR-155, as they are activated during chronic inflammatory conditions. In particular, miR-146b suppresses the production of inflammatory factors and its overexpression counteracts the activation of NFkB [36,37], whereas miR-221 is involved in the macrophagic phase [38]. MiR-146b is also called dystrophin-targeting miRNAs (DTM) because it downregulates dystrophin by binding to its 3 untranslated region (UTR) and it is induced by inflammation [39].…”

Section: Discussionmentioning

confidence: 99%

MiRNAs, Myostatin, and Muscle MRI Imaging as Biomarkers of Clinical Features in Becker Muscular Dystrophy

2020

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Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by dystrophin gene mutations. The phenotype and evolution of this muscle disorder are extremely clinical variable. In the last years, circulating biomarkers have acquired remarkable importance in their use as noninvasive biological indicators of prognosis and in monitoring muscle disease progression, especially when associated to muscle MRI imaging. We investigated the levels of circulating microRNAs (myo-miRNAs and inflammatory miRNAs) and of the proteins follistatin (FSTN) and myostatin (GDF-8) and compared results with clinical and radiological imaging data. In eight BMD patients, including two cases with evolving lower extremity weakness treated with deflazacort, we evaluated the expression level of 4 myo-miRNAs (miR-1, miR-206, miR-133a, and miR-133b), 3 inflammatory miRNAs (miR-146b, miR-155, and miR-221), FSTN, and GDF-8 proteins. In the two treated cases, there was pronounced posterior thigh and leg fibrofatty replacement assessed by muscle MRI by Mercuri score. The muscle-specific miR-206 was increased in all patients, and inflammatory miR-221 and miR-146b were variably elevated. A significant difference in myostatin expression was observed between steroid-treated and untreated patients. This study suggests that microRNAs and myostatin protein levels could be used to better understand the progression and management of the disease.

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miR-221-3p Drives the Shift of M2-Macrophages to a Pro-Inflammatory Function by Suppressing JAK3/STAT3 Activation

Cited by 100 publications

References 75 publications

miR-155 Contributes to the Immunoregulatory Function of Human Mesenchymal Stem Cells

miR-155 Contributes to the Immunoregulatory Function of Human Mesenchymal Stem Cells

Diagnostic Values of miR-221-3p in Serum and Cerebrospinal Fluid for Post-Stroke Depression and Analysis of Risk Factors

MiRNAs, Myostatin, and Muscle MRI Imaging as Biomarkers of Clinical Features in Becker Muscular Dystrophy

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