Interleukin-17 (IL-17)-induced MicroRNA 873 (miR-873) Contributes to the Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting A20 Ubiquitin-editing Enzyme

Liu, Xiaomei; He, Fengxia; Pang, Rongrong; Zhao, Dan; Qiu, Wen; Shan, Kai; Zhang, Jing; Lu, Yaxin; Li, Yan; Wang, Yingwei

doi:10.1074/jbc.m114.577429

Cited by 74 publications

(87 citation statements)

References 46 publications

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“…Many studies have demonstrated that the blockade of proinflammatory cytokines production in astrocytes can attenuate the damage of MS/EAE [19-21]. …”

Section: Discussionmentioning

confidence: 99%

“…Primary astrocytes from 0- to 1-day-old C57BL/6 mice were established as previously described [19]. Briefly, the cerebral cortices freed of meninges were dissected, minced and digested.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were housed in clean plastic cages with the temperature of 25 ± 1 ºC and humidity of 55-65 % and maintained under specific pathogen-free conditions. EAE models were induced according to our previously published procedure [19]. Briefly, 6- to 8-wk-old C57BL/6 female mice randomly divided into two groups (n=10 each group): One was injected by s.c. immunization with 200 µg MOG 35-55 peptide emulsified in complete Freund’s adjuvant (CFA, Sigma) containing 5 mg/ml heat-killed mycobacterium tuberculosis (H37Ra strain, Difco).…”

Section: Methodsmentioning

confidence: 99%

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Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Liu

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes. Methods: we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml). 12 lncRNAs were validated through real-time PCR. Gene ontology and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. Results: Differentially expressed 3300 lncRNAs and 3250 mRNAs were in the brain tissues of EAE mice, and 3748 lncRNAs and 3332 mRNAs were in activated astrocytes. Notably, there were 2 co-up-regulated lncRNAs and 3 co-down-regulated lncRNAs both in the brain tissues of EAE mice and in activated astrocytes, including Gm14005, Gm12478, mouselincRNA1117, AK080435, and mouselincRNA0681, which regulate the ER calcium flux kinetics, zinc finger protein and cell apoptosis. Similarly, there were 7 mRNAs co-up-regulated and 2 mRNAs co-down-regulated both in vivo and in vitro. Gene ontology and KEGG pathway analysis showed that the biological functions of differentially expressed mRNAs were associated with metabolism, development and inflammation. The results of realtime PCR validation were consistent with the data from the microarrays. Conclusions: Our data uncovered the expression profiles of lncRNAs and mRNAs in vivo and in vitro, which may help delineate the mechanisms of astrocyte activation during MS/EAE process.

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“…Many studies have demonstrated that the blockade of proinflammatory cytokines production in astrocytes can attenuate the damage of MS/EAE [19-21]. …”

Section: Discussionmentioning

confidence: 99%

“…Primary astrocytes from 0- to 1-day-old C57BL/6 mice were established as previously described [19]. Briefly, the cerebral cortices freed of meninges were dissected, minced and digested.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Liu

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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“…Based on the reference literature [14, 21, 22], 0-2-days-old C57BL/6 mice were used. After sacrifice, the mice were soaked in 75% ethanol for 3-5 min, and the heads were cut off under sterile conditions with ophthalmic scissors.…”

Section: Methodsmentioning

confidence: 99%

“…IL-17 is a family of proinflammatory cytokines that consists of six ligands (IL-17A, B, C, D, E and F) that are produced by a subset of Th17 cells and that bind to their associated heteromeric transmembrane receptors (IL-17RA, B, C, D and E). Because they lack IL-17 and the IL-17 receptor, mice are less susceptible to the experimental induction of autoimmune encephalomyelitis (EAE) induction [12-14]. IL-17-specific inhibition attenuates inflammation, which suggests that IL-17 signaling plays an important role in the effector stage of EAE [15].…”

Section: Introductionmentioning

confidence: 99%

The Effects of miR-136-5p-Mediated Regulation of A20 in Astrocytes from Cultured Spinal Cord Cultured Cells In Vitro

Peng

Shi

Zhao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study focused on investigating the regulatory mechanism of miR-136-5p in mouse astrocytes stimulated with interleukin-17(IL-17). Methods: C57BL/6 mouse astrocytes were stimulated with IL-17 (100ng/ml) for various periods of time (0-48 hours) and at various doses (0-200 ng), and the expression levels of inflammatory cytokine and chemokine genes (IL-6, TNF-α, MCP-1, MCP-5 and MIP-2) were then detected by real-time PCR. The expression of the A20 gene was measured with real-time PCR in cells that were stimulated with IL-17 (50 ng/ml) for various periods of time (0-48 hours). C57BL/6 mouse astrocytes were transfected with Ctrl-anti-miR-136-5p or LNA -anti-miR-136-5p for 48 h. Thereafter, the cells were stimulated with or without IL-17 (50ng/ml) for 6 h. The level of A20 protein (TNFα-induced protein 3, TNFAIP3) was detected by Western blot analysis. Results: (1) Compared with the DMEM control group, within six hours, IL-17 stimulation significantly increased the expression levels of inflammatory cytokine and chemokine genes and clearly decreased the expression level of the A20 protein. (2) Without IL-17 stimulation, the expression level of the miR-136-5p gene was significantly decreased, whereas in the miR-136-5p-inhibition group, the A20 protein expression was elevated. IL-17 stimulation slightly decreased the expression of the A20 protein in the miR-136-5p-inhibition group, but it was still slightly higher than in the control group. Conclusion: This study demonstrated that miR-136-5p affected the expression of A20 in IL-17-stimulated astrocytes.

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MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

Liu

Feng

Yang

et al. 2018

Glia

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Th17 cells and interleukin‐17 (IL‐17) have been found to play an important role in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response to IL‐17, reactive astrocytes accompany with immune cells infiltration and axonal damage in MS/EAE. However, the role and the regulatory mechanism of IL‐17‐activated astrocytes in inflammation and in the EAE process still remain largely unknown. Here, we elucidated that miR‐409‐3p and miR‐1896, as co‐upregulated microRNAs in activated astrocytes and in EAE mice, targeted suppressor of cytokine signaling proteins 3 (SOCS3). Overexpression of miR‐409‐3p or miR‐1896 significantly reduced SOCS3 expression and increased phosphorylation of STAT3 as well as induced the inflammatory cytokines production (IL‐1β, IL‐6, IP‐10, MCP‐1, and KC), CD4+T cells migration and demyelination, in turn aggravating EAE development. Importantly, the effects of co‐overexpression of miR‐409‐3p and miR‐1896 in vitro or in vivo are strongly co‐operative. In contrast, simultaneously silenced miR‐409‐3p and miR‐1896 co‐operatively ameliorates inflammation and demyelination in the central nervous system of EAE mice. Collectively, our findings highlight that miR‐409‐3p and miR‐1896 co‐ordinately promote the production of inflammatory cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance reactive astrocyte‐directed chemotaxis of CD4+T cells, leading to aggravate pathogenesis in EAE mice. Co‐inhibition of miR‐409‐3p and miR‐1896 may be a therapeutic target for treating MS and neuroinflammation.

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Interleukin-17 (IL-17)-induced MicroRNA 873 (miR-873) Contributes to the Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting A20 Ubiquitin-editing Enzyme

Cited by 74 publications

References 46 publications

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

The Effects of miR-136-5p-Mediated Regulation of A20 in Astrocytes from Cultured Spinal Cord Cultured Cells In Vitro

MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

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