miRNA‑146a attenuates inflammation in an in�vitro spinal cord injury model via inhibition of TLR4 signaling

Tan, Ying; Yu, Longtan; Zhang, Chunming; Chen, Kebing; Lu, Junfan; Tan, Liang

doi:10.3892/etm.2018.6645

Cited by 25 publications

(25 citation statements)

References 13 publications

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“…PGE 2 has been found to play a wide range of roles in acute and chronic injury of CNS [52], such as contributing to excitotoxic and ischemic neuronal cell death [53], or neuronal protection [54, 55], depending on its interacting receptor(s). With respect to its function in modulating inflammation in the context of pathophysiological conditions, PGE 2 has been demonstrated to exert both proinflammatory and immunodepressive actions.…”

Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury

Zhang

Zhou

Chen

et al. 2019

J Neuroinflammation

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Background Astrocytes have been shown to produce several pro- and anti-inflammatory cytokines to maintain homeostasis of microenvironment in response to vast array of CNS insults. Some inflammation-related cytokines are responsible for regulating such cell events. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that can be inducibly expressed in the lesioned spinal cord. Unknown is whether MIF can facilitate the production of immunosuppressive factors from astrocytes to tune milieu following spinal cord injury. Methods Following establishment of contusion SCI rat model, correlation of PGE 2 synthesis-related protein levels with that of MIF was assayed by Western blot. ELISA assay was used to detect production of PGE 2 , TNF-α, IL-1β, and IL-6. Immunohistochemistry was performed to observe colocalization of COX2 with GFAP- and S100β-positive astrocytes. The primary astrocytes were treated by various inhibitors to validate relevant signal pathway. Results The protein levels of MIF and COX2, but not of COX1, synchronously increased following spinal cord injury. Treatment of MIF inhibitor 4-IPP to the lesion sites significantly reduced the expression of COX2, mPGES-1, and as a consequence, the production of PGE 2 . Astrocytes responded robustly to the MIF interference, by which regulated MAPK/COX2/PGE 2 signal pathway through coupling with the CD74 membrane receptor. MIF-induced production of PGE 2 from astrocytes was able to suppress production of TNF-α, but boosted production of IL-1β and IL-6 in LPS-activated macrophages. Conclusion Collectively, these results reveal a novel function of MIF-mediated astrocytes, which fine-tune inflammatory microenvironment to maintain homeostasis. These suggest an alternative therapeutic strategy for CNS inflammation. Electronic supplementary material The online version of this article (10.1186/s12974-019-1468-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury

Zhang

Zhou

Chen

et al. 2019

J Neuroinflammation

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“…BV-2 cells were treated with LPS (Sigma-Aldrich, St. Louis, MO, U.S.A.) at a concentration of 100 ng/ml for 4 h at 37 • C as previously reported [32].…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

Wan

Tao

et al. 2020

Bioscience Reports

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Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.

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“…an in vitro cell model of SCI in PC12 cells was established according to a previous study (33). In brief, PC12 cells were subjected to lipopolysaccharide (LPS; 100 ng/ml) for 4 h at 37˚C.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Chen

Qin

2020

Mol Med Report

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Micrornas (mirs) play an important role in the development and progression of spinal cord injury (Sci). The role of mir-138-5p in Sci was investigated in the present study. The anti-inflammatory effects of miR-138-5p and underlying mechanisms were investigated in an Sci rat model and in vitro model. reverse transcription-quantitative Pcr (rT-qPcr) was used to examine the expression of mir-138-5p in the Sci in vivo and in vitro models, as well as patients with Sci; it was found that miR-138-5p was significantly upregulated in Sci. Bioinformatics and dual-luciferase reporter assays were performed to predict and confirm the binding sites between mir-138-5p and the 3'untranslated region of sirtuin 1 (SirT1). Then, the expression of SirT1 was detected via rT-qPcr and western blotting, indicating downregulation of SIRT1 in SCI. PC12 cells were transfected with miR-138-5p inhibitor, inhibitor control or miR-138-5p inhibitor + SIRT1 small interfering RNA for 48 h, and then subjected to lipopolysaccharide (100 ng/ml) treatment for 4 h. Then, MTT assay, flow cytometry and eliSa experiments were performed to analyze cell viability, apoptosis, and the levels of tumor necrosis factor-α, interleukin (il)-1β and il-6. Findings suggested that downregulation of miR-138-5p increased PC12 cell viability, inhibited cell apoptosis and attenuated proinflammatory responses, which may result in amelioration of Sci. However, all these effects were reversed by SIRT1 knockdown. Finally, it was observed that miR-138-5p altered the related protein expression of the PTen/aKT pathway. These results indicated that miR-138-5p could regulate inflammatory responses and cell apoptosis in SCI models by modulating the PTEN/AKT signaling pathway via SirT1, thus playing an important role in the development of Sci. collectively, the present study demonstrated that miR-138-5p may be a novel therapeutic target for the treatment of Sci. Materials and methodsClinical samples. a total of 18 serum specimens from patients with Sci (age range, 27-58 years; 12 male patients and 6 female MicroRNA-138-5p regulates the development of spinal cord injury by targeting SIRT1 JincHuan cHen and ruJie Qin department of Spine Surgery, The First People's Hospital of lianyungang, lianyungang, Jiangsu 222000, P.r. china

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miRNA‑146a attenuates inflammation in an in�vitro spinal cord injury model via inhibition of TLR4 signaling

Cited by 25 publications

References 13 publications

Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury

Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

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