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Publication : Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines.

First Author  Lu YC Year  2009
Journal  J Immunol Volume  182
Issue  11 Pages  7212-21
PubMed ID  19454718 Mgi Jnum  J:148852
Mgi Id  MGI:3847019 Doi  10.4049/jimmunol.0802971
Citation  Lu YC, et al. (2009) Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines. J Immunol 182(11):7212-21
abstractText  TLR stimulation triggers a signaling pathway via MyD88 and IL-1R-associated kinase 4 that is essential for proinflammatory cytokine induction. Although NF-kappaB has been shown to be one of the key transcriptional regulators of these cytokines, evidence suggests that other factors may also be important. In this study, we showed that MyD88-deficient macrophages have defective c-Rel activation, which has been linked to IL-12p40 induction, but not IL-6 or TNF-alpha. We also investigated other transcription factors and showed that C/EBPbeta and C/EBPdelta expression was limited in MyD88- or IL-1R-associated kinase 4-deficient macrophages treated with LPS. Importantly, the absence of both C/EBPbeta and C/EBPdelta resulted in the impaired induction of proinflammatory cytokines stimulated by several TLR ligands. Our results identify c-Rel and C/EBPbeta/delta as important transcription factors in a MyD88-dependent pathway that regulate the induction of proinflammatory cytokines.
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