Differential Role for c-Rel and C/EBPβ/δ in TLR-Mediated Induction of Proinflammatory Cytokines
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 i...
Saved in:
Published in | The Journal of immunology (1950) Vol. 182; no. 11; pp. 7212 - 7221 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.06.2009
|
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | Current address: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh PA 15261. Current address: Department of Molecular and Cellular Biology, Nippon Boehringer Ingelheim Company Ltd., Hygo, Japan. Current address: Macfarlane Burnet Institute for Medical Research and Public Health, Prahran, VIC 3004, Australia. Current address: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan. |
ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.0802971 |