FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2327755877> ?p ?o ?g. }

• W2327755877 endingPage "239" @default.
• W2327755877 startingPage "239" @default.
• W2327755877 abstract "The transcription factor NF-κB induces expression of a variety of genes involved in mediating the immune response, including cytokines, chemokines, and adhesion molecules (reviewed in Gut 1998;43:856-60 ). The NFκB family is comprised of several genes whose products associate to form dimers, most commonly consisting of p65 and p50 in human cells. The dimer complex is maintained in an inactive state in the cellular cytoplasm by association with the inhibitory protein IκB. Upon phosphorylation by kinases, known as κ kinases, IκB undergoes ubiquitination and degradation, thereby allowing NF-κB to translocate into the nucleus and activate transcription. Due to the significance of NF-κB in immune regulation, perhaps it is not surprising that several anti-inflammatory agents can exert their effect by altering NF-κB signaling (Fig 1). For example, corticosteroids inhibit NF-κB activity by inducing production of the inhibitory binding protein IκB. Wahl et al. (J Clin Invest 1998;101:1163-174 ) discovered that sulfasalazine interfers with NF-κB activation by preventing IκB degradation. These findings are of particular interest because several studies implicate NF-κB activation in mediating chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, and gastroenteric infections including Helicobacter pylori.Fig. 1: Aspirin inhibits NF-κB activation. Aspirin inhibits phosphorylation of IκB by IκB kinase, thereby preventing degradation of the inhibitory protein. NF-κB is sequestered in the cytoplasm in an inactive state and nuclear transcription of target genes does not occur.It is generally considered that the therapeutic effect of aspirin resides in its ability to inhibit prostaglandin synthesis. However, previous studies demonstrated that aspirin also blocks activation of NF-κB. In the November 5th issue of Nature (1998;396:77-80 ), Yin et al. identify the mechanism by which aspirin and sodium salicylates inhibit NF-κB. In the presence of stimulation by the potent cytokine tumor necrosis factor-alpha (TNF-α), aspirin specifically inhibits the kinase responsible for phosphorylating IκB, IκB kinase-β. Therefore, NF-κB is maintained in its inactive form complexed with IκB in the cytoplasm and transcription of genes involved in the inflammatory response is abrogated. Thus, an additional anti-inflammatory mechanism for aspirin has been delineated. As with many immunomodulatory therapies, the therapeutic efficacy of the agents is hampered by unwanted toxicity, in part due to nonspecific activities. Aspirin is no exception. Therefore, the delineation of the precise pathways by which drugs exert their effects should allow for the development of improved therapeutic agents that can be directed towards altering specific pathways. The pleitrophic signals that NF-κB regulates indicate a level of complexity that we are only beginning to understand. Therefore, the potential development of novel therapeutic interventions with reduced toxicity for the management of chronic inflammatory conditions is awaited with anticipation. Nicola L. Jones, MD, FRCPC Philip M. Sherman, MD, FRCPC The Hospital for Sick Children, University of Toronto, Toronto, Canada" @default.
• W2327755877 created "2016-06-24" @default.
• W2327755877 creator A5030726218 @default.
• W2327755877 creator A5083599998 @default.
• W2327755877 date "1999-03-01" @default.
• W2327755877 modified "2023-09-23" @default.
• W2327755877 title "The Mechanism Underlying Aspirin's Anti-inflammatory Effects: A New Twist to an Old Tale" @default.
• W2327755877 doi "https://doi.org/10.1097/00005176-199903000-00002" @default.
• W2327755877 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10067718" @default.
• W2327755877 hasPublicationYear "1999" @default.
• W2327755877 type Work @default.
• W2327755877 sameAs 2327755877 @default.
• W2327755877 citedByCount "0" @default.
• W2327755877 crossrefType "journal-article" @default.
• W2327755877 hasAuthorship W2327755877A5030726218 @default.
• W2327755877 hasAuthorship W2327755877A5083599998 @default.
• W2327755877 hasBestOaLocation W23277558771 @default.
• W2327755877 hasConcept C100175707 @default.
• W2327755877 hasConcept C104317684 @default.
• W2327755877 hasConcept C11960822 @default.
• W2327755877 hasConcept C123298856 @default.
• W2327755877 hasConcept C13373296 @default.
• W2327755877 hasConcept C184235292 @default.
• W2327755877 hasConcept C203014093 @default.
• W2327755877 hasConcept C25602115 @default.
• W2327755877 hasConcept C2777730290 @default.
• W2327755877 hasConcept C2779730028 @default.
• W2327755877 hasConcept C55493867 @default.
• W2327755877 hasConcept C62478195 @default.
• W2327755877 hasConcept C71924100 @default.
• W2327755877 hasConcept C86339819 @default.
• W2327755877 hasConcept C86803240 @default.
• W2327755877 hasConcept C8891405 @default.
• W2327755877 hasConcept C95444343 @default.
• W2327755877 hasConcept C98270193 @default.
• W2327755877 hasConceptScore W2327755877C100175707 @default.
• W2327755877 hasConceptScore W2327755877C104317684 @default.
• W2327755877 hasConceptScore W2327755877C11960822 @default.
• W2327755877 hasConceptScore W2327755877C123298856 @default.
• W2327755877 hasConceptScore W2327755877C13373296 @default.
• W2327755877 hasConceptScore W2327755877C184235292 @default.
• W2327755877 hasConceptScore W2327755877C203014093 @default.
• W2327755877 hasConceptScore W2327755877C25602115 @default.
• W2327755877 hasConceptScore W2327755877C2777730290 @default.
• W2327755877 hasConceptScore W2327755877C2779730028 @default.
• W2327755877 hasConceptScore W2327755877C55493867 @default.
• W2327755877 hasConceptScore W2327755877C62478195 @default.
• W2327755877 hasConceptScore W2327755877C71924100 @default.
• W2327755877 hasConceptScore W2327755877C86339819 @default.
• W2327755877 hasConceptScore W2327755877C86803240 @default.
• W2327755877 hasConceptScore W2327755877C8891405 @default.
• W2327755877 hasConceptScore W2327755877C95444343 @default.
• W2327755877 hasConceptScore W2327755877C98270193 @default.
• W2327755877 hasIssue "3" @default.
• W2327755877 hasLocation W23277558771 @default.
• W2327755877 hasLocation W23277558772 @default.
• W2327755877 hasOpenAccess W2327755877 @default.
• W2327755877 hasPrimaryLocation W23277558771 @default.
• W2327755877 hasRelatedWork W1501881225 @default.
• W2327755877 hasRelatedWork W1963709111 @default.
• W2327755877 hasRelatedWork W2047852425 @default.
• W2327755877 hasRelatedWork W2050345435 @default.
• W2327755877 hasRelatedWork W2145842985 @default.
• W2327755877 hasRelatedWork W2201194340 @default.
• W2327755877 hasRelatedWork W2318334567 @default.
• W2327755877 hasRelatedWork W2377917104 @default.
• W2327755877 hasRelatedWork W4297063097 @default.
• W2327755877 hasRelatedWork W1921622578 @default.
• W2327755877 hasVolume "28" @default.
• W2327755877 isParatext "false" @default.
• W2327755877 isRetracted "false" @default.
• W2327755877 magId "2327755877" @default.
• W2327755877 workType "article" @default.