Lack of TLR4 modifies the miRNAs profile and attenuates inflammatory signaling pathways
| Autor: | Francisco García-García, Raúl Pérez-Moraga, Consuelo Guerri, Juan R. Ureña-Peralta |
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| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_treatment Biochemistry Immune Receptors Mice 0302 clinical medicine Cell Signaling Medicine and Health Sciences Membrane Receptor Signaling Technology Regulations Receptor Toll-like Receptors Immune Response Cerebral Cortex Mice Knockout Immune System Proteins Multidisciplinary Organic Compounds Immune Receptor Signaling Cell biology Nucleic acids Chemistry Cytokine Physical Sciences Medicine Cytokines Female medicine.symptom Signal transduction Research Article Signal Transduction Science Policy Science Immunology Inflammation Biology Proinflammatory cytokine 03 medical and health sciences Signs and Symptoms Genetics medicine Animals Non-coding RNA Neuroinflammation Natural antisense transcripts Biology and life sciences Ethanol Organic Chemistry Chemical Compounds Proteins Cell Biology TLR7 Gene regulation Mice Inbred C57BL Toll-Like Receptor 4 MicroRNAs 030104 developmental biology Gene Expression Regulation Alcohols TLR4 RNA Gene expression Clinical Medicine Transcriptome 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 8, p e0237066 (2020) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0237066 |
| Popis: | TLR4 is a member of the toll-like receptors (TLR) immune family, which are activated by lipopolysaccharide, ethanol or damaged tissue, among others, by triggering proinflammatory cytokines release and inflammation. Lack of TLR4 protects against inflammatory processes and neuroinflammation linked with several neuropathologies. By considering that miRNAs are key post-transcriptional regulators of the proteins involved in distinct cellular processes, including inflammation, this study aimed to assess the impact of the miRNAs profile in mice cortices lacking the TLR4 response. Using mice cerebral cortices and next-generation sequencing (NGS), the findings showed that lack of TLR4 significantly reduced the quantity and diversity of the miRNAs expressed in WT mice cortices. The results also revealed a significant down-regulation of the miR-200 family, while cluster miR-99b/let-7e/miR-125a was up-regulated in TLR4-KO vs. WT. The bioinformatics and functional analyses demonstrated that TLR4-KO presented the systematic depletion of many pathways closely related to the immune system response, such as cytokine and interleukin signaling, MAPK and ion Channels routes, MyD88 pathways, NF-κβ and TLR7/8 pathways. Our results provide new insights into the molecular and biological processes associated with the protective effects of TLR-KO against inflammatory damage and neuroinflammation, and reveal the relevance of the TLR4 receptors response in many neuropathologies. |
| Databáze: | OpenAIRE |
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