Differential role for c-Rel and C/EBPβ/δ in TLR-mediated induction of proinflammatory cytokines

Yong Chen Lu, Ira Kim, Elizabeth Lye, Fang Shen, Nobutaka Suzuki, Shinobu Suzuki, Steve Gerondakis, Shizuo Akira, Sarah L. Gaffen, Wen Chen Yeh, Pamela S. Ohashi

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78 Citations (Scopus)

Abstract

TLR stimulation triggers a signaling pathway via MyD88 and IL-1R-associated kinase 4 that is essential for proinflammatory cytokine induction. Although NF-κB 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-α. We also investigated other transcription factors and showed that C/EBPβ and C/EBPδ expression was limited in MyD88- or IL-1R-associated kinase 4-deficient macrophages treated with LPS. Importantly, the absence of both C/EBPβ and C/EBPδ resulted in the impaired induction of proinflammatory cytokines stimulated by several TLR ligands. Our results identify c-Rel and C/EBPβ/δ as important transcription factors in a MyD88-dependent pathway that regulate the induction of proinflammatory cytokines.

Original languageEnglish
Pages (from-to)7212-7221
Number of pages10
JournalJournal of Immunology
Volume182
Issue number11
DOIs
Publication statusPublished - 1 Jun 2009
Externally publishedYes

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