| First Author | Bode KA | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 4 | Pages | 2176-84 |
| PubMed ID | 19201871 | Mgi Jnum | J:144791 |
| Mgi Id | MGI:3831949 | Doi | 10.4049/jimmunol.0802560 |
| Citation | Bode KA, et al. (2009) Kinetic of RelA activation controls magnitude of TLR-mediated IL-12p40 induction. J Immunol 182(4):2176-84 |
| abstractText | IL-12 is a crucial cytokine for dendritic cell-mediated induction of Th 1 cell differentiation. TLR ligands induce IL-12 to differing extents. Stimulation of dendritic cells allowed for the differentiation of three groups of TLRs; potency to induce IL-12 decreased in the order of TLR7/9, TLR3/4, and TLR1/2/6 stimulation. The MAPK, PI3K, and IRF (IFN regulatory factor) signaling pathways could be ruled out to be the cause for the differences in IL-12p40 induction. However, we observed that stimulation of dendritic cells with different TLR ligands resulted in striking differences in the kinetics of NF-kappaB activation. LPS induced a rapid but short-lived activation of RelA, whereas CpG-DNA stimulation resulted in prolonged RelA activity at the IL-12p40 promoter. Only TLR2 and TLR4 ligands were capable of inducing S536 phosphorylation of RelA, which has been proposed to be responsible for early termination of NF-kappaB activation. It is suggested that differences in the kinetics of a common TLR signaling module affect the biological response patterns of various TLRs, with IL-12p40 being a gene that needs prolonged NF-kappaB activation. |
