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C5a-regulated CCAAT/Enhancer-binding Proteins beta and delta Are Essential in Fc gamma Receptor-mediated Inflammatory Cytokine and Chemokine Production in Macrophages

  1. Author:
    Yan, C. G.
    Zhu, M.
    Staiger, J.
    Johnson, P. F.
    Gao, H. W.

  2. Author Address

    [Yan, Chunguang; Gao, Hongwei] Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med,Sch Med, Boston, MA 02115 USA. [Zhu, Mei] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Staiger, Jennifer] Mt St Marys Univ, Dept Sci, Sch Nat Sci & Math, Emmitsburg, MD 21727 USA. [Johnson, Peter F.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Frederick, MD 21702 USA.;Gao, HW (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol,Sch Med, 20 Shattuck St, Boston, MA 02115 USA;hgao@zeus.bwh.harvard.edu
    1. Year: 2012
    2. Date: Jan
  2. Journal: Journal of Biological Chemistry
    1. 287
    2. 5
    3. Pages: 3217-3230
  4. Type of Article: Article
  5. ISSN: 0021-9258
  1. Abstract:

    CCAAT/enhancer-binding protein beta (C/EBP beta) and C/EBP delta are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBP beta and -delta in inflammatory responses elicited by Fc gamma receptor (Fc gamma R) activation. Here we show that C/EBP beta and -delta activation are induced in IgG immune complex (IC)-treated macrophages. The increased expression of C/EBP beta and -delta occurred at both mRNA and protein levels. Furthermore, induction of C/EBP beta and -delta was mediated, to a large extent, by activating Fc gamma Rs. Using siRNA-mediated knockdown as well as macrophages deficient for C/EBP beta and/or -delta, we demonstrate that C/EBP beta and -delta play a critical role in the production of TNF-alpha, MIP-2, and MIP-1 alpha in IgG IC-stimulated macrophages. Moreover, both ERK1/2 and p38 MAPK are involved in C/EBP induction and TNF-alpha, MIP-2, and MIP-1 alpha production induced by IgGIC. We provide the evidence that C5a regulates IgGIC-induced inflammatory responses by enhancing ERK1/2 and p38 MAPK activities as well as C/EBP beta and -delta activities. Collectively, these data suggest that C/EBP beta and -delta are key regulators for Fc gamma R-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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External Sources

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  2. DOI: 10.1074/jbc.M111.280834
  3. View record in Web of Science®
  4. WOS: 000300295100027

Library Notes

  1. Fiscal Year: FY2011-2012
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