FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2036645992> ?p ?o ?g. }

• W2036645992 endingPage "14914" @default.
• W2036645992 startingPage "14904" @default.
• W2036645992 abstract "Microglia rapidly mount an inflammatory response to pathogens in the central nervous system (CNS). Heparan sulfate proteoglycans (HSPGs) have been attributed various roles in inflammation. To elucidate the relevance of microglial HSPGs in a pro-inflammatory response we isolated microglia from mice overexpressing heparanase (Hpa-tg), the HS-degrading endoglucuronidase, and challenged them with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS-stimulation, the LPS-receptor cluster-of-differentiation 14 (CD14) and Toll-like receptor 4 (TLR4; essential for the LPS response) were similarly expressed in Ctrl and Hpa-tg microglia. However, compared with Ctrl microglia, Hpa-tg cells released significantly less tumor necrosis factor-α (TNFα), essentially failed to up-regulate interleukin-1β (IL1β) and did not initiate synthesis of proCD14. Isolated primary astroyctes expressed TLR4, but notably lacked CD14 and in contrast to microglia, LPS challenge induced a similar TNFα response in Ctrl and Hpa-tg astrocytes, while neither released IL1β. The astrocyte TNFα-induction was thus attributed to CD14-independent TLR4 activation and was unaffected by the cells HS status. Equally, the suppressed LPS-response in Hpa-tg microglia indicated a loss of CD14-dependent TLR4 activation, suggesting that microglial HSPGs facilitate this process. Indeed, confocal microscopy confirmed interactions between microglial HS and CD14 in LPS-stimulated microglia and a potential HS-binding motif in CD14 was identified. We conclude that microglial HSPGs facilitate CD14-dependent TLR4 activation and that heparanase can modulate this mechanism. Microglia rapidly mount an inflammatory response to pathogens in the central nervous system (CNS). Heparan sulfate proteoglycans (HSPGs) have been attributed various roles in inflammation. To elucidate the relevance of microglial HSPGs in a pro-inflammatory response we isolated microglia from mice overexpressing heparanase (Hpa-tg), the HS-degrading endoglucuronidase, and challenged them with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS-stimulation, the LPS-receptor cluster-of-differentiation 14 (CD14) and Toll-like receptor 4 (TLR4; essential for the LPS response) were similarly expressed in Ctrl and Hpa-tg microglia. However, compared with Ctrl microglia, Hpa-tg cells released significantly less tumor necrosis factor-α (TNFα), essentially failed to up-regulate interleukin-1β (IL1β) and did not initiate synthesis of proCD14. Isolated primary astroyctes expressed TLR4, but notably lacked CD14 and in contrast to microglia, LPS challenge induced a similar TNFα response in Ctrl and Hpa-tg astrocytes, while neither released IL1β. The astrocyte TNFα-induction was thus attributed to CD14-independent TLR4 activation and was unaffected by the cells HS status. Equally, the suppressed LPS-response in Hpa-tg microglia indicated a loss of CD14-dependent TLR4 activation, suggesting that microglial HSPGs facilitate this process. Indeed, confocal microscopy confirmed interactions between microglial HS and CD14 in LPS-stimulated microglia and a potential HS-binding motif in CD14 was identified. We conclude that microglial HSPGs facilitate CD14-dependent TLR4 activation and that heparanase can modulate this mechanism." @default.
• W2036645992 created "2016-06-24" @default.
• W2036645992 creator A5001998362 @default.
• W2036645992 creator A5018345023 @default.
• W2036645992 creator A5027380526 @default.
• W2036645992 creator A5070348421 @default.
• W2036645992 creator A5088174305 @default.
• W2036645992 date "2015-06-01" @default.
• W2036645992 modified "2023-10-05" @default.
• W2036645992 title "Microglial Heparan Sulfate Proteoglycans Facilitate the Cluster-of-Differentiation 14 (CD14)/Toll-like Receptor 4 (TLR4)-Dependent Inflammatory Response" @default.
• W2036645992 cites W1646206347 @default.
• W2036645992 cites W1766658148 @default.
• W2036645992 cites W1784761870 @default.
• W2036645992 cites W1918739823 @default.
• W2036645992 cites W1965068547 @default.
• W2036645992 cites W1965520866 @default.
• W2036645992 cites W1971246306 @default.
• W2036645992 cites W1977195767 @default.
• W2036645992 cites W1978525572 @default.
• W2036645992 cites W1985640778 @default.
• W2036645992 cites W1995458780 @default.
• W2036645992 cites W1995586746 @default.
• W2036645992 cites W1998152154 @default.
• W2036645992 cites W2002330167 @default.
• W2036645992 cites W2006721652 @default.
• W2036645992 cites W2009523990 @default.
• W2036645992 cites W2011229547 @default.
• W2036645992 cites W2011473936 @default.
• W2036645992 cites W2019676172 @default.
• W2036645992 cites W2024070670 @default.
• W2036645992 cites W2029880457 @default.
• W2036645992 cites W2031251046 @default.
• W2036645992 cites W2033818437 @default.
• W2036645992 cites W2037189769 @default.
• W2036645992 cites W2042851093 @default.
• W2036645992 cites W2050320551 @default.
• W2036645992 cites W2053962613 @default.
• W2036645992 cites W2056402897 @default.
• W2036645992 cites W2058012473 @default.
• W2036645992 cites W2061463538 @default.
• W2036645992 cites W2065053912 @default.
• W2036645992 cites W2065819179 @default.
• W2036645992 cites W2066665372 @default.
• W2036645992 cites W2069132198 @default.
• W2036645992 cites W2070105244 @default.
• W2036645992 cites W2074987771 @default.
• W2036645992 cites W2076316745 @default.
• W2036645992 cites W2078985378 @default.
• W2036645992 cites W2090465196 @default.
• W2036645992 cites W2093711314 @default.
• W2036645992 cites W2103901522 @default.
• W2036645992 cites W2105301755 @default.
• W2036645992 cites W2108684523 @default.
• W2036645992 cites W2112644797 @default.
• W2036645992 cites W2113075523 @default.
• W2036645992 cites W2123355863 @default.
• W2036645992 cites W2124343538 @default.
• W2036645992 cites W2125279675 @default.
• W2036645992 cites W2145938600 @default.
• W2036645992 cites W2147617210 @default.
• W2036645992 cites W2160805000 @default.
• W2036645992 cites W4294349425 @default.
• W2036645992 cites W4361960923 @default.
• W2036645992 cites W44384258 @default.
• W2036645992 doi "https://doi.org/10.1074/jbc.m114.634337" @default.
• W2036645992 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4463438" @default.
• W2036645992 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25869127" @default.
• W2036645992 hasPublicationYear "2015" @default.
• W2036645992 type Work @default.
• W2036645992 sameAs 2036645992 @default.
• W2036645992 citedByCount "43" @default.
• W2036645992 countsByYear W20366459922016 @default.
• W2036645992 countsByYear W20366459922017 @default.
• W2036645992 countsByYear W20366459922018 @default.
• W2036645992 countsByYear W20366459922019 @default.
• W2036645992 countsByYear W20366459922020 @default.
• W2036645992 countsByYear W20366459922021 @default.
• W2036645992 countsByYear W20366459922022 @default.
• W2036645992 countsByYear W20366459922023 @default.
• W2036645992 crossrefType "journal-article" @default.
• W2036645992 hasAuthorship W2036645992A5001998362 @default.
• W2036645992 hasAuthorship W2036645992A5018345023 @default.
• W2036645992 hasAuthorship W2036645992A5027380526 @default.
• W2036645992 hasAuthorship W2036645992A5070348421 @default.
• W2036645992 hasAuthorship W2036645992A5088174305 @default.
• W2036645992 hasBestOaLocation W20366459921 @default.
• W2036645992 hasConcept C136449434 @default.
• W2036645992 hasConcept C169760540 @default.
• W2036645992 hasConcept C170493617 @default.
• W2036645992 hasConcept C17991360 @default.
• W2036645992 hasConcept C185592680 @default.
• W2036645992 hasConcept C203014093 @default.
• W2036645992 hasConcept C2776070231 @default.
• W2036645992 hasConcept C2776709828 @default.
• W2036645992 hasConcept C2776914184 @default.
• W2036645992 hasConcept C2777542381 @default.
• W2036645992 hasConcept C2778513237 @default.
• W2036645992 hasConcept C2778754761 @default.

• next