Toll-Like Receptor 4 (TLR4) Expression Affects Schwann Cell Behavior in vitro

Zhang, Huanhuan; Shao, Zhiwei; Zhu, Yun; Shi, Lingyu; Li, Zhihao; Hou, Rui; Zhang, Chunwang; Yao, Dengbing

doi:10.1038/s41598-018-28516-5

Cited by 11 publications

(9 citation statements)

References 45 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The experimental procedure was employed as described previously (9). In short, the cells were resuspended in DMEM at a concentration of 5 Â 10 4 cells/ well.…”

Section: Transwell Cell Migration Assaymentioning

confidence: 99%

“…Insight into its intrinsic mechanism reveals that E6020, a novel synthetic toll-like receptor 4 (TLR4) agonist, is capable of accelerating infiltration of SCs and remyelination in the rat spinal cord (8). TLR4 is expressed both in innate immune cells and in central nervous system cells, and has been reported to participate in nervous system development and modulate the adult neuronal precursor cell differentiation and proliferation (9). Recently reported study has offered proof that the expression of TLR4 can affect lipopolysaccharide (LPS)-induced inflammatory cytokine production by SCs (10).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sepsis Activates the TLR4/MyD88 Pathway in Schwann Cells to Promote Infiltration of Macrophages, Thereby Impeding Neuromuscular Function

Liu

Bai

et al. 2020

Shock

View full text Add to dashboard Cite

Introduction: Sepsis is a kind of maladjustment response to bacterial infection and activation of coagulation, which can induce neuromuscular dysfunction. However, there is scarce of experimental evidence about the relationship between Schwann cells (SCs) and sepsis in neuromuscular dysfunction. We therefore set out to identify the potential role of SCs in sepsis-induced neuromuscular dysfunction and to explore the underlying molecular mechanism. Methods: Primary SCs were isolated from the left hind limb sciatic nerve of sepsis mice, which was constructed by cecal ligation and puncture. Then, the SCs were infected with adenovirus encoding toll-like receptor 4 (TLR4), MyD88, or IL-1R (with lipopolysaccharide stimulation), and the Raw 264.7 macrophages were injected with adenovirus with CCR2 silencing (with mMCP-1 stimulation). Further investigation of the interleukin 1 beta (IL-1b) and macrophage cationic peptide 1 (MCP-1) expressions, we followed reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay techniques, the F4/80 and Ki67 expressions was observed by immunofluorescence staining, while the expressions of CCR2, FAK/p-FAK, nuclear factor-kB (NFkB)/p-NFkB, and ERK1/2/p-ERK1/2 were determined by Western blot analysis. Last, but not the least, the cell migration ability and cell proliferation ability were detected by Transwell assay and Flow cytometry respectively. Results: Our results showed that in sepsis mice, the TLR4/MyD88/ERK pathway was activated in SCs, which triggered the cells to secrete IL-1b and MCP-1. The secreted IL-1b bound with IL-1b receptor on the surface of SCs, thereby activating the IL-1b/IL-1R/MyD88/ERK pathway and further promoting the secretion of MCP-1 by SCs. MCP-1 was found to bind to CCR2 on the surface of Raw264.7 macrophages to activate the TLR4/MyD88/ERK pathway which caused the inhibition of neuromuscular function. Conclusion: Sepsis significantly promotes the infiltration of macrophages by activating the TLR4/MyD88 pathway in SCs, thereby impeding neuromuscular function. Consistently, our study provides a novel concept in the area of neuromuscular dysfunction therapeutics following sepsis.

show abstract

“…The experimental procedure was employed as described previously (9). In short, the cells were resuspended in DMEM at a concentration of 5 Â 10 4 cells/ well.…”

Section: Transwell Cell Migration Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sepsis Activates the TLR4/MyD88 Pathway in Schwann Cells to Promote Infiltration of Macrophages, Thereby Impeding Neuromuscular Function

Liu

Bai

et al. 2020

Shock

View full text Add to dashboard Cite

show abstract

“…Pain reduction in patients with PNI is an important area of focus in medicine. Previous studies have demonstrated that Schwann cells serve an important role in promoting axonal regeneration, myelin repair and functional recovery in neuroregeneration (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Identification of adhesion‑associated DNA methylation patterns in the peripheral nervous system

et al. 2020

View full text Add to dashboard Cite

Schwann cells are unique glial cells in the peripheral nervous system. These cells provide a range of cytokines and nutritional factors to maintain axons and support axonal regeneration. However, little is known concerning adhesion-associated epigenetic changes that occur in Schwann cells after peripheral nerve injury (PNI). In the present study, adhesion-associated DNA methylation biomarkers were assessed between normal and injury peripheral nerve. Specifically, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were obtained from adult Wistar rats. After the Schwann cells were identified, proliferation and adhesion assays were used to assess differences between NSCs and ASCs. Methylated DNA immunoprecipitation-sequencing and bioinformatics analysis were used to identify and analyze the differentially methylated genes. Reverse transcription-quantitative PCR was performed to assess the expression levels of adhesion-associated genes. In the present study, the proliferation and adhesion assays demonstrated that ASCs had a more robust proliferative activity and adhesion compared with NSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify methylation-associated biological processes and signaling pathways. Protein-protein interaction network analysis revealed that Fyn, Efna1, Jak2, Vav3, Flt4, Epha7, Crk, Kitlg, Ctnnb1 and Ptpn11 were potential markers for Schwann cell adhesion. The expression levels of several adhesion-associated genes, such as vinculin, BCAR1 scaffold protein, collagen type XVIII α1 chain and integrin subunit β6, in ASCs were altered compared with those in NSCs. The current study analyzed adhesion-associated DNA methylation patterns of Schwann cells and identified candidate genes that may potentially regulate Schwann cell adhesion in Wistar rats before and after PNI.

show abstract

“…Lipopolysaccharide-induced inflammatory cytokine production by SCs is dependent upon TLR4 expression. In vitro data showed that TLR4 expression is upregulated after sciatic nerve injury of rat and modulation of its expression increased relative gene expression of proinflammatory molecules such as c-Jun and extracellular signal-regulated kinase (ERK) [32]. In our in vitro model, TRIAM reduced significantly TLR4 expression implying an anti-inflammatory potential of SCs after TRIAM treatment.…”

Section: Discussionmentioning

confidence: 80%

Intrathecal triamcinolone acetonide exerts anti-inflammatory effects on Lewis rat experimental autoimmune neuritis and direct anti-oxidative effects on Schwann cells

Pitarokoili

Sgodzai

Grüter

et al. 2019

J Neuroinflammation

View full text Add to dashboard Cite

Background Corticosteroids dominate in the treatment of chronic autoimmune neuropathies although long-term use is characterized by devastating side effects. Methods We introduce the intrathecal application of the synthetic steroid triamcinolone (TRIAM) as a novel therapeutic option in experimental autoimmune neuritis in Lewis rats Results After immunization with neuritogenic P2 peptide, we show a dose-dependent therapeutic effect of one intrathecal injection of 0.3 or 0.6 mg/kg TRIAM on clinical and electrophysiological parameters of neuritis with a lower degree of inflammatory infiltrates (T cells and macrophages) and demyelination in the sciatic nerve. In vitro studies in Schwann cell cultures showed an increased expression of IL-1 receptor antagonist and reduced expression of Toll-like receptor 4 after incubation with TRIAM as well as a protective effect of TRIAM against oxidative stress after H 2 O 2 exposure. Conclusion Intrathecal TRIAM application could be a novel immunomodulatory and potentially neuroprotective option for autoimmune neuropathies with a direct effect on Schwann cells.

show abstract

Toll-Like Receptor 4 (TLR4) Expression Affects Schwann Cell Behavior in vitro

Cited by 11 publications

References 45 publications

Sepsis Activates the TLR4/MyD88 Pathway in Schwann Cells to Promote Infiltration of Macrophages, Thereby Impeding Neuromuscular Function

Sepsis Activates the TLR4/MyD88 Pathway in Schwann Cells to Promote Infiltration of Macrophages, Thereby Impeding Neuromuscular Function

Identification of adhesion‑associated DNA methylation patterns in the peripheral nervous system

Intrathecal triamcinolone acetonide exerts anti-inflammatory effects on Lewis rat experimental autoimmune neuritis and direct anti-oxidative effects on Schwann cells

Contact Info

Product

Resources

About