C5a-regulated CCAAT/enhancer-binding proteins β and δ are essential in Fcγ receptor-mediated inflammatory cytokine and chemokine production in macrophages.

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.
AuthorsChunguang Yan, Mei Zhu, Jennifer Staiger, Peter F Johnson, Hongwei Gao
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 5 Pg. 3217-30 (Jan 27 2012) ISSN: 1083-351X [Electronic] United States
PMID22147692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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
  • 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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