Control of the Inflammatory Macrophage Transcriptional Signature by miR-155

Jablonski, Kyle; Gaudet, Andrew D.; Amici, Stephanie A.; Popovich, Phillip G.; Guerau-de-Arellano, Mireia

doi:10.1371/journal.pone.0159724

Cited by 118 publications

(106 citation statements)

References 73 publications

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“…It is of necessity to note that miRNAs (eg, miR‐155 and miR‐146) are also involved in macrophage polarization . MiR‐155 is the most highly upregulated miRNA in LPS/IFN‐γ‐treated macrophages . However, IL‐4 does not affect miR‐155 expression .…”

Section: Mechanisms Whereby Melatonin Regulates Macrophage Polarizationmentioning

confidence: 99%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

Journal of Pineal Research

145

126

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Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

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Section: Mechanisms Whereby Melatonin Regulates Macrophage Polarizationmentioning

confidence: 99%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

Journal of Pineal Research

145

126

View full text Add to dashboard Cite

show abstract

“…Although macrophage-derived exosomes have been studied most extensively in the context of tumor associated macrophages; it is possible that changes in overall WAT exosome-miRNA profiles in lean compared to obese samples partially derive from M2 vs. M1 macrophages in the AT. With regards to miRNA released from WAT macrophages, miR-155 is upregulated in M1-like macrophages and seems to control macrophage inflammatory phenotype [90]. miR-330-5p is also inflammatory, and its inhibition promotes M2 polarization [69].…”

Section: Counterpoint To the Proinflammatory Adipose Tissue Macrophagmentioning

confidence: 99%

Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

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A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts continue seeking interventions to mitigate obesity-associated AT inflammation, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g. beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology. prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7]. Thus, a better understanding of adipose tissue (AT), the organ that expands the most in size during obesity, should provide solutions to this health concern.When discussing AT, white adipose tissue (WAT) is most commonly considered; however, other types of AT, brown adipose tissue (BAT) and beige AT also exist.Adipocytes in WAT and BAT are generated from unique progenitors. WAT stores excess energy in the form of triglycerides. BAT can store small amounts of triglycerides; however, its primary role is to burn fatty acids to generate heat. Beige fat has brown-like properties but is transiently present in WAT depots (especially subcutaneous) upon beta-adrenergic stimulation. Regulation of all three of these fat depots is critically important for lipid and energy homeostasis.WAT consists of spatially distinct beds: visceral, omental, subcutaneous, perivascular, epicardial, and many others. These depots serve to cushion organs they BAT is localized primarily in subscapular regions in rodents, and was only discovered in adult humans in the past decade [10,11]. BAT has a characteristic brown appearance grossly, and is easily distinguished from WAT. This distinctive color is due to the presence of concentrated mitochondria within each brown adipocyte, accompanied by high iron concentrations required for activation of the electron transport chain during beta-oxidation. High expression of uncoupling protein 1 (UCP-1) causes this beta-oxidation to result in generation of heat rather than ATP (thermogenesis), thus assistin...

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“…In macrophages and microglia, damage-or pathogen-associated molecular patterns bind toll-like receptors and elicit inflammatory signaling pathways (Graff et al, 2012;Freilich et al, 2013;. Blocking miR-155-5p limits these inflammatory responses in macrophages (Cai et al, 2012;Nazari-Jahantigh et al, 2012;Jablonski et al, 2016) and microglia (Cardoso et al, 2012). Although the effects of miR-155-5p on axon growth are unclear, indirect evidence and in silico prediction models (Lewis et al, 2003;John et al, 2004;O'Connell et al, 2009;Liu et al, 2011b) suggest that miR-155-5p could bind various RAG-related mRNAs, which could restrict the synthesis of proteins that enhance axon growth.…”

Section: Introductionmentioning

confidence: 99%

miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

Gaudet

Mandrekar-Colucci

Hall

et al. 2016

Journal of Neuroscience

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Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155-5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ϳ40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ϳ50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI.

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Control of the Inflammatory Macrophage Transcriptional Signature by miR-155

Cited by 118 publications

References 73 publications

Melatonin in macrophage biology: Current understanding and future perspectives

Melatonin in macrophage biology: Current understanding and future perspectives

Contributions of innate type 2 inflammation to adipose function

miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

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