FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2316621204> ?p ?o ?g. }

• W2316621204 endingPage "S42" @default.
• W2316621204 startingPage "S42" @default.
• W2316621204 abstract "Intervertebral disc degeneration is a leading cause of chronic low back pain (LBP), but how degeneration contributes to LBP is poorly understood. Nerve growth factor (NGF) is upregulated in disc degeneration. The presence of NGF may promote disc innervation, neuronal sensitization and low back pain, making NGF a possible therapeutic target. However, the mechanisms underlying the dysregulation of NGF during degeneration are poorly understood. During disc degeneration proteoglycans and other extra-cellular matrix (ECM) proteins are degraded and fragmented. ECM fragments can act as endogenous danger signal ligands for toll-like receptors, which were originally characterized in the innate immune system. TLR activation induces cytokine and chemokine expression, and could regulate a sterile inflammation in disc degeneration. NGF is often upregulated in inflammation, therefore we hypothesized that TLR activation leads to NGF overexpression in intervertebral disc cells. To test this hypothesis we treated human disc cells with IL-1β (control), peptidoglycan (PGN, TLR2 agonist) and lipopolysaccharide (LPS, TLR4 agonist) and evaluated NGF gene and protein expression. IL-1β and PGN treatment increased NGF gene expression after 6, 12 and 24 hours and protein secretion after 24 and 48 hours, while LPS had little effect. To confirm that PGN is acting through TLR2, we knocked down TLR2 with siRNA, which greatly decreased PGN-induced NGF expression. We evaluated which signaling pathways regulate NGF by western blot and found PGN treatment of disc cells increased p38 MAPK and NF-κB phosphorylation. Using small molecule signaling inhibitors, we found p38 inhibition had little effect on PGN induction of NGF, while NF-κB inhibition blocked NGF upregulation. Taken together, these results suggest that TLR2 activation regulates NGF through NF-κB signaling. Identification of this new mechanism of NGF regulation in intervertebral disc cells could lead to the development of new therapeutic strategies for LBP associated with disc degeneration. Intervertebral disc degeneration is a leading cause of chronic low back pain (LBP), but how degeneration contributes to LBP is poorly understood. Nerve growth factor (NGF) is upregulated in disc degeneration. The presence of NGF may promote disc innervation, neuronal sensitization and low back pain, making NGF a possible therapeutic target. However, the mechanisms underlying the dysregulation of NGF during degeneration are poorly understood. During disc degeneration proteoglycans and other extra-cellular matrix (ECM) proteins are degraded and fragmented. ECM fragments can act as endogenous danger signal ligands for toll-like receptors, which were originally characterized in the innate immune system. TLR activation induces cytokine and chemokine expression, and could regulate a sterile inflammation in disc degeneration. NGF is often upregulated in inflammation, therefore we hypothesized that TLR activation leads to NGF overexpression in intervertebral disc cells. To test this hypothesis we treated human disc cells with IL-1β (control), peptidoglycan (PGN, TLR2 agonist) and lipopolysaccharide (LPS, TLR4 agonist) and evaluated NGF gene and protein expression. IL-1β and PGN treatment increased NGF gene expression after 6, 12 and 24 hours and protein secretion after 24 and 48 hours, while LPS had little effect. To confirm that PGN is acting through TLR2, we knocked down TLR2 with siRNA, which greatly decreased PGN-induced NGF expression. We evaluated which signaling pathways regulate NGF by western blot and found PGN treatment of disc cells increased p38 MAPK and NF-κB phosphorylation. Using small molecule signaling inhibitors, we found p38 inhibition had little effect on PGN induction of NGF, while NF-κB inhibition blocked NGF upregulation. Taken together, these results suggest that TLR2 activation regulates NGF through NF-κB signaling. Identification of this new mechanism of NGF regulation in intervertebral disc cells could lead to the development of new therapeutic strategies for LBP associated with disc degeneration." @default.
• W2316621204 created "2016-06-24" @default.
• W2316621204 creator A5025845330 @default.
• W2316621204 creator A5028696068 @default.
• W2316621204 creator A5050561253 @default.
• W2316621204 creator A5062579944 @default.
• W2316621204 creator A5064048333 @default.
• W2316621204 creator A5075413088 @default.
• W2316621204 creator A5081739623 @default.
• W2316621204 date "2015-04-01" @default.
• W2316621204 modified "2023-10-17" @default.
• W2316621204 title "(266) TLR2 activation induces NGF gene and protein expression via NF-κB in human intervertebral disc cells" @default.
• W2316621204 doi "https://doi.org/10.1016/j.jpain.2015.01.183" @default.
• W2316621204 hasPublicationYear "2015" @default.
• W2316621204 type Work @default.
• W2316621204 sameAs 2316621204 @default.
• W2316621204 citedByCount "0" @default.
• W2316621204 crossrefType "journal-article" @default.
• W2316621204 hasAuthorship W2316621204A5025845330 @default.
• W2316621204 hasAuthorship W2316621204A5028696068 @default.
• W2316621204 hasAuthorship W2316621204A5050561253 @default.
• W2316621204 hasAuthorship W2316621204A5062579944 @default.
• W2316621204 hasAuthorship W2316621204A5064048333 @default.
• W2316621204 hasAuthorship W2316621204A5075413088 @default.
• W2316621204 hasAuthorship W2316621204A5081739623 @default.
• W2316621204 hasBestOaLocation W23166212041 @default.
• W2316621204 hasConcept C104317684 @default.
• W2316621204 hasConcept C126322002 @default.
• W2316621204 hasConcept C127561419 @default.
• W2316621204 hasConcept C13373296 @default.
• W2316621204 hasConcept C170493617 @default.
• W2316621204 hasConcept C2776070231 @default.
• W2316621204 hasConcept C2776914184 @default.
• W2316621204 hasConcept C2778423431 @default.
• W2316621204 hasConcept C2781236682 @default.
• W2316621204 hasConcept C51551487 @default.
• W2316621204 hasConcept C55493867 @default.
• W2316621204 hasConcept C57074206 @default.
• W2316621204 hasConcept C62478195 @default.
• W2316621204 hasConcept C71924100 @default.
• W2316621204 hasConcept C86803240 @default.
• W2316621204 hasConcept C95444343 @default.
• W2316621204 hasConceptScore W2316621204C104317684 @default.
• W2316621204 hasConceptScore W2316621204C126322002 @default.
• W2316621204 hasConceptScore W2316621204C127561419 @default.
• W2316621204 hasConceptScore W2316621204C13373296 @default.
• W2316621204 hasConceptScore W2316621204C170493617 @default.
• W2316621204 hasConceptScore W2316621204C2776070231 @default.
• W2316621204 hasConceptScore W2316621204C2776914184 @default.
• W2316621204 hasConceptScore W2316621204C2778423431 @default.
• W2316621204 hasConceptScore W2316621204C2781236682 @default.
• W2316621204 hasConceptScore W2316621204C51551487 @default.
• W2316621204 hasConceptScore W2316621204C55493867 @default.
• W2316621204 hasConceptScore W2316621204C57074206 @default.
• W2316621204 hasConceptScore W2316621204C62478195 @default.
• W2316621204 hasConceptScore W2316621204C71924100 @default.
• W2316621204 hasConceptScore W2316621204C86803240 @default.
• W2316621204 hasConceptScore W2316621204C95444343 @default.
• W2316621204 hasIssue "4" @default.
• W2316621204 hasLocation W23166212041 @default.
• W2316621204 hasOpenAccess W2316621204 @default.
• W2316621204 hasPrimaryLocation W23166212041 @default.
• W2316621204 hasRelatedWork W1897355343 @default.
• W2316621204 hasRelatedWork W2004726042 @default.
• W2316621204 hasRelatedWork W2046649601 @default.
• W2316621204 hasRelatedWork W2049435255 @default.
• W2316621204 hasRelatedWork W2086513193 @default.
• W2316621204 hasRelatedWork W2103573355 @default.
• W2316621204 hasRelatedWork W2270349401 @default.
• W2316621204 hasRelatedWork W2904803842 @default.
• W2316621204 hasRelatedWork W2922302300 @default.
• W2316621204 hasRelatedWork W4200092334 @default.
• W2316621204 hasVolume "16" @default.
• W2316621204 isParatext "false" @default.
• W2316621204 isRetracted "false" @default.
• W2316621204 magId "2316621204" @default.
• W2316621204 workType "article" @default.