Matches in SemOpenAlex for { <https://semopenalex.org/work/W2086890953> ?p ?o ?g. }
- W2086890953 endingPage "2086" @default.
- W2086890953 startingPage "2074" @default.
- W2086890953 abstract "CD40Ligand (CD40L) represents a strong endogenous danger signal associated with chronic inflammatory disease. CD40L induces activation of antigen-presenting cells (APCs) such as DCs, monocytes, B-cells and endothelial cells. However, CD40 activation alone, whilst inducing IL-10 production, is insufficient to induce interleukin (IL)-12p70 release in human APCs suggesting that additional cytokine signals (e.g. GM-CSF, IL-4 or IFN-γ) are required for the induction of a pro-inflammatory cytokine profile. We demonstrate that IFN-γ-induced Janus kinase 1 (JAK1) enhances CD40-induced IL-12p70 release whilst simultaneously inhibiting IL-10 synthesis, resulting in a pro-inflammatory phenotype of CD40L-activated dendritic cells (DCs). JAK2 mediated enhancing effects on IL-12p70 but did not inhibit IL-10 release, whereas Tyk2 mediated inhibitory effects on IL-12p70 release in this system. The mechanism by which complementary IFN-γ/JAK activities affect IL-12p70 production involves STAT1 activation and de novo induction of interferon-responsive factors (IRF)-1 and IRF-8. Simultaneously, JAK1 was unique in inhibiting IL-10 synthesis via STAT1 and IRF-8 with both transcription factors binding to the IL-10 promoter. We demonstrate that CD40- and JAK/STAT/IRF-signalling pathways are strictly complementary for the induction of a pro-inflammatory cytokine profile in human APCs. This suggests that a number of CD40 effects in chronic inflammatory diseases might be weakened by targeting JAK/STAT." @default.
- W2086890953 created "2016-06-24" @default.
- W2086890953 creator A5013029612 @default.
- W2086890953 creator A5031642616 @default.
- W2086890953 creator A5036354220 @default.
- W2086890953 creator A5047882707 @default.
- W2086890953 creator A5051573848 @default.
- W2086890953 creator A5059935166 @default.
- W2086890953 creator A5066232501 @default.
- W2086890953 creator A5066532230 @default.
- W2086890953 creator A5067574718 @default.
- W2086890953 creator A5070027273 @default.
- W2086890953 creator A5075375896 @default.
- W2086890953 creator A5085146093 @default.
- W2086890953 date "2010-12-01" @default.
- W2086890953 modified "2023-10-16" @default.
- W2086890953 title "IFN-γ activated JAK1 shifts CD40-induced cytokine profiles in human antigen-presenting cells toward high IL-12p70 and low IL-10 production" @default.
- W2086890953 cites W1483584036 @default.
- W2086890953 cites W1568945049 @default.
- W2086890953 cites W1905620693 @default.
- W2086890953 cites W1965694516 @default.
- W2086890953 cites W1969702741 @default.
- W2086890953 cites W1975490463 @default.
- W2086890953 cites W1977672571 @default.
- W2086890953 cites W1979676829 @default.
- W2086890953 cites W1983485321 @default.
- W2086890953 cites W1987448779 @default.
- W2086890953 cites W1998601064 @default.
- W2086890953 cites W2001635017 @default.
- W2086890953 cites W2002507218 @default.
- W2086890953 cites W2013958910 @default.
- W2086890953 cites W2024381893 @default.
- W2086890953 cites W2031060692 @default.
- W2086890953 cites W2033172475 @default.
- W2086890953 cites W2045884774 @default.
- W2086890953 cites W2052907030 @default.
- W2086890953 cites W2056854005 @default.
- W2086890953 cites W2060004314 @default.
- W2086890953 cites W2065160550 @default.
- W2086890953 cites W2068659248 @default.
- W2086890953 cites W2070629020 @default.
- W2086890953 cites W2084178693 @default.
- W2086890953 cites W2093294507 @default.
- W2086890953 cites W2098123605 @default.
- W2086890953 cites W2101492664 @default.
- W2086890953 cites W2102204735 @default.
- W2086890953 cites W2107954314 @default.
- W2086890953 cites W2111608779 @default.
- W2086890953 cites W2116624889 @default.
- W2086890953 cites W2134756173 @default.
- W2086890953 cites W2144950102 @default.
- W2086890953 cites W2156313733 @default.
- W2086890953 cites W2157278565 @default.
- W2086890953 cites W2159987374 @default.
- W2086890953 cites W2165965510 @default.
- W2086890953 cites W2167192576 @default.
- W2086890953 cites W2267540851 @default.
- W2086890953 cites W276577763 @default.
- W2086890953 doi "https://doi.org/10.1016/j.bcp.2010.07.040" @default.
- W2086890953 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20709027" @default.
- W2086890953 hasPublicationYear "2010" @default.
- W2086890953 type Work @default.
- W2086890953 sameAs 2086890953 @default.
- W2086890953 citedByCount "22" @default.
- W2086890953 countsByYear W20868909532012 @default.
- W2086890953 countsByYear W20868909532013 @default.
- W2086890953 countsByYear W20868909532014 @default.
- W2086890953 countsByYear W20868909532015 @default.
- W2086890953 countsByYear W20868909532016 @default.
- W2086890953 countsByYear W20868909532017 @default.
- W2086890953 countsByYear W20868909532020 @default.
- W2086890953 countsByYear W20868909532021 @default.
- W2086890953 countsByYear W20868909532022 @default.
- W2086890953 crossrefType "journal-article" @default.
- W2086890953 hasAuthorship W2086890953A5013029612 @default.
- W2086890953 hasAuthorship W2086890953A5031642616 @default.
- W2086890953 hasAuthorship W2086890953A5036354220 @default.
- W2086890953 hasAuthorship W2086890953A5047882707 @default.
- W2086890953 hasAuthorship W2086890953A5051573848 @default.
- W2086890953 hasAuthorship W2086890953A5059935166 @default.
- W2086890953 hasAuthorship W2086890953A5066232501 @default.
- W2086890953 hasAuthorship W2086890953A5066532230 @default.
- W2086890953 hasAuthorship W2086890953A5067574718 @default.
- W2086890953 hasAuthorship W2086890953A5070027273 @default.
- W2086890953 hasAuthorship W2086890953A5075375896 @default.
- W2086890953 hasAuthorship W2086890953A5085146093 @default.
- W2086890953 hasBestOaLocation W20868909532 @default.
- W2086890953 hasConcept C112392421 @default.
- W2086890953 hasConcept C130523297 @default.
- W2086890953 hasConcept C149532602 @default.
- W2086890953 hasConcept C154317977 @default.
- W2086890953 hasConcept C157333092 @default.
- W2086890953 hasConcept C170493617 @default.
- W2086890953 hasConcept C180361614 @default.
- W2086890953 hasConcept C185592680 @default.
- W2086890953 hasConcept C202751555 @default.
- W2086890953 hasConcept C203014093 @default.
- W2086890953 hasConcept C2775960820 @default.