WFRF:(Kichev A.)
Sökning: WFRF:(Kichev A.) > Implicating Recepto...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04786naa a2200577 4500 | |
| 001 | oai:gup.ub.gu.se/256012 | |
| 003 | SwePub | |
| 008 | 240528s2017 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://gup.ub.gu.se/publication/2560122 URI |
| 024 | 7 | a https://doi.org/10.1159/0004642442 DOI |
| 040 | a (SwePub)gu | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Kichev, A.4 aut |
| 245 | 1 0 | a Implicating Receptor Activator of NF-kappa B (RANK)/RANK Ligand Signalling in Microglial Responses to Toll-Like Receptor Stimuli |
| 264 | c 2017-04-13 | |
| 264 | 1 | b S. Karger AG,c 2017 |
| 520 | a Inflammation in the perinatal brain caused by maternal or intrauterine fetal infection is now well established as an important contributor to the development of perinatal brain injury. Exposure to inflammatory products can impair perinatal brain development and act as a risk factor for neurological dysfunction, cognitive disorders, cerebral palsy, or preterm birth. Pre-exposure to inflammation significantly exacerbates brain injury caused by hypoxic/ischaemic insult. Tumour necrosis factor (TNF) is a family of cytokines largely involved in inflammation signalling. In our previous study, we identified the importance of TNF-related apoptosis-inducing ligand (TRAIL) signalling in the development of perinatal brain injury. We observed a significant increase in the expression levels of a soluble decoy receptor for TRAIL, osteoprotegerin (OPG). Besides TRAIL, OPG is able to bind the receptor activator of the NF-kappa B (RANK) ligand (RANKL) and inhibit its signalling. The function of the RANK/RANKL/OPG system in the brain has not come under much scrutiny. The aim of this research study was to elucidate the role of RANK, RANKL, and OPG in microglial responses to the pro-inflammatory stimuli lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (Poly I: C). Here, we show that RANK signalling is important for regulating the activation of the BV2 microglial cell line. We found that LPS treatment causes a significant decrease in the expression of RANK in the BV2 cell line while significantly increasing the expression of OPG, Toll-like receptor (TLR) 3, and the adaptor proteins MyD88 and TRIF. We found that pretreatment of BV2 cells with RANKL for 24 h before the LPS or Poly I: C exposure decreases the expression of inflammatory markers such as inducible nitric oxide synthase and cyclooxygenase. This is accompanied by a decreased expression of the TLR adaptor proteins MyD88 and TRIF, which we observed after RANKL treatment. Similar results were obtained in our experiments with primary mouse microglia. Using recently developed CRISPR/Cas9 technology, we generated a BV2 cell line lacking RANK (RANK(-/-) BV2). We showed that most effects of RANKL pretreatment were abolished, thereby proving the specificity of this effect. Taken together, these findings suggest that RANK signalling is important for modulating the inflammatory activation of microglial cells to a moderate level, and that RANK attenuates TLR3/TLR4 signalling. (C) 2017 The Author(s) Published by S. Karger AG, Basel | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
| 653 | a Hypoxia-ischaemia | |
| 653 | a Inflammation | |
| 653 | a Microglia | |
| 653 | a RANK | |
| 653 | a RANKL | |
| 653 | a Osteoprotegerin | |
| 653 | a Toll-like receptors | |
| 653 | a central-nervous-system | |
| 653 | a apoptosis-inducing ligand | |
| 653 | a osteoprotegerin | |
| 653 | a ligand | |
| 653 | a ischemic brain | |
| 653 | a inflammation | |
| 653 | a disease | |
| 653 | a cells | |
| 653 | a lipopolysaccharide | |
| 653 | a cultures | |
| 653 | a protein | |
| 653 | a Developmental Biology | |
| 653 | a Neurosciences & Neurology | |
| 700 | 1 | a Eede, P.4 aut |
| 700 | 1 | a Gressens, P.4 aut |
| 700 | 1 | a Thornton, C.4 aut |
| 700 | 1 | a Hagberg, Henrik,d 1955u Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology4 aut0 (Swepub:gu)xhaghe |
| 710 | 2 | a Göteborgs universitetb Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi4 org |
| 773 | 0 | t Developmental Neuroscienced : S. Karger AGg 39:1-4, s. 192-206q 39:1-4<192-206x 0378-5866x 1421-9859 |
| 856 | 4 | u https://www.karger.com/Article/Pdf/464244 |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/256012 |
| 856 | 4 8 | u https://doi.org/10.1159/000464244 |
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