Differential Role for c-Rel and C/EBP beta/delta in TLR-Mediated Induction of Proinflammatory Cytokines

Lu, YC; Kim, I; Lye, E; Shen, F; Suzuki, N; Suzuki, S; Gerondakis, S; Akira, S; Gaffen, SL; Yeh, WC; Ohashi, PS

Author(s): Lu, YC; Kim, I; Lye, E; Shen, F; Suzuki, N; Suzuki, S; Gerondakis, S; Akira, S; Gaffen, SL; Yeh, WC; Ohashi, PS;
Details: Publication Year 2009-06-01,Volume 182,Issue #11,Page 7212-7221
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: TLR stimulation triggers a signaling pathway via MyD88 and IL-1R-associated kinase 4 that is essential for proinflammatory cytokine induction. Although NF-kappa B 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/EBP beta and C/EBP delta expression was limited in MyD88- or IL-1R-associated kinase 4-deficient macrophages treated with LPS. Importantly, the absence of both C/EBP beta and C/EBP delta resulted in the impaired induction of proinflammatory cytokines stimulated by several TLR ligands. Our results identify c-Rel and C/EBP beta/delta as important transcription factors in a MyD88-dependent pathway that regulate the induction of proinflammatory cytokines. The Journal of Immunology, 2009, 182: 7212-7221.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: NF-KAPPA-B; CCAAT/ENHANCER BINDING-PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; LEUCINE-ZIPPER PROTEINS; BETA-DEFICIENT MICE; TOLL-LIKE RECEPTORS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSES
Publisher's Version: https://doi.org/10.4049/jimmunol.0802971
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-06-01 12:00:00