Abstract |
CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPδ are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBPβ and -δ in inflammatory responses elicited by Fcγ receptor (FcγR) activation. Here we show that C/EBPβ and -δ activation are induced in IgG immune complex (IC)-treated macrophages. The increased expression of C/EBPβ and -δ occurred at both mRNA and protein levels. Furthermore, induction of C/EBPβ and -δ was mediated, to a large extent, by activating FcγRs. Using siRNA-mediated knockdown as well as macrophages deficient for C/EBPβ and/or -δ, we demonstrate that C/EBPβ and -δ play a critical role in the production of TNF-α, MIP-2, and MIP-1α in IgG IC-stimulated macrophages. Moreover, both ERK1/2 and p38 MAPK are involved in C/EBP induction and TNF-α, MIP-2, and MIP-1α production induced by IgG IC. We provide the evidence that C5a regulates IgG IC-induced inflammatory responses by enhancing ERK1/2 and p38 MAPK activities as well as C/EBPβ and -δ activities. Collectively, these data suggest that C/EBPβ and -δ are key regulators for FcγR-mediated induction of cytokines and chemokines in macrophages. Furthermore, C/EBPs may play an important regulatory role in IC-associated inflammatory responses.
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Authors | Chunguang Yan, Mei Zhu, Jennifer Staiger, Peter F Johnson, Hongwei Gao |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 287
Issue 5
Pg. 3217-30
(Jan 27 2012)
ISSN: 1083-351X [Electronic] United States |
PMID | 22147692
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- CCAAT-Enhancer-Binding Protein-beta
- Chemokines
- Receptors, IgG
- CCAAT-Enhancer-Binding Protein-delta
- Complement C5a
- Mitogen-Activated Protein Kinase 3
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Animals
- CCAAT-Enhancer-Binding Protein-beta
(genetics, metabolism)
- CCAAT-Enhancer-Binding Protein-delta
(genetics, metabolism)
- Cell Line
- Chemokines
(biosynthesis)
- Complement C5a
(genetics, metabolism)
- Inflammation
(genetics, metabolism)
- MAP Kinase Signaling System
(physiology)
- Mice
- Mitogen-Activated Protein Kinase 3
(genetics, metabolism)
- Receptors, IgG
(genetics, metabolism)
- p38 Mitogen-Activated Protein Kinases
(genetics, metabolism)
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