Downregulated expression of miR-223 promotes Toll-like receptor-activated inflammatory responses in macrophages by targeting RhoB

Zhang, Ningjie; Fu, Liyao; Bu, Yanhong; Yao, Yao; Wang, Yongjun

doi:10.1016/j.molimm.2017.08.026

Cited by 43 publications

(33 citation statements)

References 29 publications

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“…Thus, IL‐6 may promote macrophage inflammatory signaling by both direct increase in STAT3 expression and by indirect inhibition of miR‐223, which targets STAT3 mRNA. Another study by Zhang and colleagues also demonstrated the regulatory function of miR‐223 in macrophages during TLR stimulation . Consistent with previous studies, TLR ligand stimulation dramatically reduced miR‐223 expression in macrophages.…”

Section: Mir‐223 In Innate Immunitysupporting

confidence: 82%

MicroRNA miR-223 as regulator of innate immunity

Yuan

Berg

Lee

et al. 2018

Journal of Leukocyte Biology

134

105

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MicroRNAs were discovered more than 2 decades ago and have profound impact on diverse biological processes. Specific microRNAs have important roles in modulating the innate immune response and their dysregulation has been demonstrated to contribute to inflammatory diseases. MiR-223 in particular, is very highly expressed and tightly regulated in hematopoietic cells. It functions as key modulator for the differentiation and activation of myeloid cells. The central role of miR-223 in myeloid cells, especially neutrophil and macrophage differentiation and activation has been studied extensively. MiR-223 contributes to myeloid differentiation by enhancing granulopoiesis while inhibiting macrophage differentiation. Uncontrolled myeloid activation has detrimental consequences in inflammatory disease. MiR-223 serves as a negative feedback mechanism controlling excessive innate immune responses in the maintenance of myeloid cell homeostasis. This review summarizes several topics covering the function of miR-223 in myeloid differentiation, neutrophil and macrophage functions, as well as in inflammatory diseases including acute respiratory distress syndrome and inflammatory bowel disease. In addition, nonmyeloid functions of miR-223 are also discussed in this review. Therapeutic enhancement of miR-223 to dampen inflammatory targets is also highlighted as potential treatment to control excessive innate immune responses during mucosal inflammation.

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Section: Mir‐223 In Innate Immunitysupporting

confidence: 82%

MicroRNA miR-223 as regulator of innate immunity

Yuan

Berg

Lee

et al. 2018

Journal of Leukocyte Biology

134

105

View full text Add to dashboard Cite

show abstract

“…32) Meanwhile, it plays a role in inhibiting inflammation and preventing indirect injury during infection. [33][34][35] Jnk signaling pathway is an important branch of the MAPK signaling pathway, and plays an important role in many physiological and pathological processes, such as cell cycle, reproduction, apoptosis, and cell stress. 36,37) Schreck, et al revealed that the activation of the Jnk signaling pathway causes p-c-jun to undergo nuclear translocation and up-regulates COX-2 expression, thereby accelerating the process of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Emodin Attenuates Lipopolysaccharide-Induced Injury via Down-Regulation of miR-223 in H9c2 Cells

Yang¹,

Jiang²,

Zhuge³

2019

Int. Heart J.

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Emodin is a natural product extracted from Rheum palmatum. There are few recent studies on emodin in the treatment of myocarditis. This study aimed to investigate the effect of emodin on lipopolysaccharide (LPS)induced inflammatory injury in cardiomyocytes. H9c2 cells were treated with 10 μM of LPS and different concentrations (0, 1, 5, 10, 15, and 20 μM) of emodin. The expression of miR-223 was changed by transient transfection. Thereafter, cell viability, apoptosis, the expression of CyclinD1 and Jnk-associated proteins, and the release of pro-inflammatory factors were assessed by cell Counting Kit-8, flow cytometry analysis, quantitative real-time polymerase chain reaction Western blot, and enzyme-linked immunosorbent assay respectively. The results showed that 20 μM of emodin significantly decreased H9c2 cells viability. LPS significantly damaged H9c2 cells, as cell viability was reduced, CyclinD1 was down-regulated, apoptosis was induced, the release of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha were increased, and the phosphorylation of Jnk and c-Jun were promoted. Emodin protected H9c2 cells against LPS-induced inflammatory injury. miR-223 expression was significantly up-regulated by LPS exposure, while emodin lessened this up-regulation. LPS-injured H9c2 cells were attenuated by the overexpression of miR-223; emodin has protective actions on LPS-injured H9c2 cells and targets. Besides, SP600125 (an inhibitor of Jnk) eliminated miR-223-modulated inflammatory injury in H9c2 cells. These data demonstrated that emodin could attenuate LPS-induced inflammatory injury and deactivate Jnk signaling pathway through down-regulation of miR-223. (Int Heart J 2019; 60: 436-443)

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“…In particular, miR-223 has been implicated in negatively regulating TLR-NFκB signaling [172]. As a potential therapeutic option, miR-223 overexpression markedly reduces pro-inflammatory cytokine production in TLR-stimulated macrophages [173,174] and limits neutrophilic inflammation [175]. Aside from regulating TLRs, miR-223 is the most abundant miRNA in platelets [176,177] and is known to regulate platelet expression of the P2Y 12 receptor [177].…”

Section: Tlr Therapeutics: Potential For Targeting Platelet-tlrs?mentioning

confidence: 99%

Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Hally

Fauteux‐Daniel

Hamzeh‐Cognasse

et al. 2020

IJMS

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While platelet function has traditionally been described in the context of maintaining vascular integrity, recent evidence suggests that platelets can modulate inflammation in a much more sophisticated and nuanced manner than previously thought. Some aspects of this expanded repertoire of platelet function are mediated via expression of Toll-like receptors (TLRs). TLRs are a family of pattern recognition receptors that recognize pathogen-associated and damage-associated molecular patterns. Activation of these receptors is crucial for orchestrating and sustaining the inflammatory response to both types of danger signals. The TLR family consists of 10 known receptors, and there is at least some evidence that each of these are expressed on or within human platelets. This review presents the literature on TLR-mediated platelet activation for each of these receptors, and the existing understanding of platelet-TLR immune modulation. This review also highlights unresolved methodological issues that potentially contribute to some of the discrepancies within the literature, and we also suggest several recommendations to overcome these issues. Current understanding of TLR-mediated platelet responses in influenza, sepsis, transfusion-related injury and cardiovascular disease are discussed, and key outstanding research questions are highlighted. In summary, we provide a resource—a “researcher’s toolkit”—for undertaking further research in the field of platelet-TLR biology.

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Downregulated expression of miR-223 promotes Toll-like receptor-activated inflammatory responses in macrophages by targeting RhoB

Cited by 43 publications

References 29 publications

MicroRNA miR-223 as regulator of innate immunity

MicroRNA miR-223 as regulator of innate immunity

Emodin Attenuates Lipopolysaccharide-Induced Injury via Down-Regulation of miR-223 in H9c2 Cells

Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

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