| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
IL-10 is an important immunoregulatory factor. However, our understanding of IL-10 gene regulation remains very limited. In this study, following up on our previous novel finding that the protooncogene c-Maf of the basic leucine zipper family of transcription factors is expressed in monocytes and macrophages, we investigate the role of c-Maf in the transcriptional regulation of IL-10 and the underlying molecular mechanism in macrophages. c-Maf-null macrophages exhibit strongly impaired IL-10 protein production and mRNA expression upon LPS stimulation. Ectopic expression of c-Maf stimulates not only exogenously transfected IL-10 promoter-driven luciferase activity in a dose-dependent manner but also enhances endogenous IL-10 gene expression stimulated by LPS. Both in vitro and in vivo experiments identify a c-Maf response element localized to nucleotides –196/–184 relative to the transcription initiation site in the IL-10 promoter. This site represents an atypical 12-O-tetradecanoate-13-acetate-responsive element for musculoaponeurotic fibrosarcoma recognition and functions as an enhancer element in a heterologous and orientation-independent manner. Furthermore, c-Maf is expressed constitutively in resting monocytes/macrophages. IL-4 can up-regulate c-Maf expression, its binding to IL-10 promoter, and dose dependently enhance IL-10 production induced by LPS; moreover, IL-4 failed to enhance LPS-induced IL-10 production in c-Maf-null macrophages. Taken together, these data demonstrate that c-Maf is an indispensable yet constitutive transcription factor for IL-10 gene expression in LPS-activated macrophages, and IL-4 modulates IL-10 production in inflammatory macrophages likely via its ability to induce c-Maf expression. Thus, this study uncovers a novel and important function of c-Maf in macrophages and elucidates its transcriptional mechanism in the regulation of IL-10 gene expression.
This article has been cited by other articles:
|
|
 |
|
  C. Pot, H. Jin, A. Awasthi, S. M. Liu, C.-Y. Lai, R. Madan, A. H. Sharpe, C. L. Karp, S.-C. Miaw, I-C. Ho, et al. Cutting Edge: IL-27 Induces the Transcription Factor c-Maf, Cytokine IL-21, and the Costimulatory Receptor ICOS that Coordinately Act Together to Promote Differentiation of IL-10-Producing Tr1 Cells J. Immunol., July 15, 2009; 183(2): 797 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Leavenworth, X. Ma, Y.-y. Mo, and M. E. Pauza SUMO Conjugation Contributes to Immune Deviation in Nonobese Diabetic Mice by Suppressing c-Maf Transactivation of IL-4 J. Immunol., July 15, 2009; 183(2): 1110 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, Y. Yang, G. Qiu, G. Lal, Z. Wu, D. E. Levy, J. C. Ochando, J. S. Bromberg, and Y. Ding c-Maf Regulates IL-10 Expression during Th17 Polarization J. Immunol., May 15, 2009; 182(10): 6226 - 6236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhang, J. Rowe, M. Kusel, A. Bosco, K. McKenna, N. de Klerk, P. D. Sly, and P. G. Holt Interleukin-10/Interleukin-5 Responses at Birth Predict Risk for Respiratory Infections in Children with Atopic Family History Am. J. Respir. Crit. Care Med., February 1, 2009; 179(3): 205 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chakrabarti, A. J. Sadler, N. Kar, H. A. Young, R. H. Silverman, and B. R. G. Williams Protein Kinase R-dependent Regulation of Interleukin-10 in Response to Double-stranded RNA J. Biol. Chem., September 12, 2008; 283(37): 25132 - 25139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Csoka, Z. H. Nemeth, L. Virag, P. Gergely, S. J. Leibovich, P. Pacher, C.-X. Sun, M. R. Blackburn, E. S. Vizi, E. A. Deitch, et al. A2A adenosine receptors and C/EBP{beta} are crucially required for IL-10 production by macrophages exposed to Escherichia coli Blood, October 1, 2007; 110(7): 2685 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dong, C. Ivascu, H.-D. Chang, P. Wu, R. Angeli, L. Maggi, F. Eckhardt, L. Tykocinski, C. Haefliger, B. Mowes, et al. IL-10 Is Excluded from the Functional Cytokine Memory of Human CD4+ Memory T Lymphocytes J. Immunol., August 15, 2007; 179(4): 2389 - 2396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Chang, B. Guo, S. E. Doyle, and G. Cheng Cutting Edge: Involvement of the Type I IFN Production and Signaling Pathway in Lipopolysaccharide-Induced IL-10 Production J. Immunol., June 1, 2007; 178(11): 6705 - 6709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Staples, T. Smallie, L. M. Williams, A. Foey, B. Burke, B. M. J. Foxwell, and L. Ziegler-Heitbrock IL-10 Induces IL-10 in Primary Human Monocyte-Derived Macrophages via the Transcription Factor Stat3 J. Immunol., April 15, 2007; 178(8): 4779 - 4785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Bella, W. Tang, A. Kraja, D. C. Rao, S. C. Hunt, M. B. Miller, V. Palmieri, M. J. Roman, D. W. Kitzman, A. Oberman, et al. Genome-Wide Linkage Mapping for Valve Calcification Susceptibility Loci in Hypertensive Sibships: The Hypertension Genetic Epidemiology Network Study Hypertension, March 1, 2007; 49(3): 453 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, D. M. Mosser, and X. Zhang Activation of the MAPK, ERK, following Leishmania amazonensis Infection of Macrophages J. Immunol., January 15, 2007; 178(2): 1077 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Flores, K. A. Diggs, L. M. Tait, and P. A. Morel IFN-{gamma} Negatively Regulates CpG-Induced IL-10 in Bone Marrow-Derived Dendritic Cells J. Immunol., January 1, 2007; 178(1): 211 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cao, X. Zhang, J. P. Edwards, and D. M. Mosser NF-{kappa}B1 (p50) Homodimers Differentially Regulate Pro- and Anti-inflammatory Cytokines in Macrophages J. Biol. Chem., September 8, 2006; 281(36): 26041 - 26050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shoemaker, M. Saraiva, and A. O'Garra GATA-3 Directly Remodels the IL-10 Locus Independently of IL-4 in CD4+ T Cells J. Immunol., March 15, 2006; 176(6): 3470 - 3479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. H. Nemeth, C. S. Lutz, B. Csoka, E. A. Deitch, S. J. Leibovich, W. C. Gause, M. Tone, P. Pacher, E. S. Vizi, and G. Hasko Adenosine Augments IL-10 Production by Macrophages through an A2B Receptor-Mediated Posttranscriptional Mechanism J. Immunol., December 15, 2005; 175(12): 8260 - 8270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Jones and R. A. Flavell Distal Enhancer Elements Transcribe Intergenic RNA in the IL-10 Family Gene Cluster J. Immunol., December 1, 2005; 175(11): 7437 - 7446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saraiva{paragraph}, J. R. Christensen, A. V. Tsytsykova, A. E. Goldfeld, S. C. Ley, D. Kioussis, and A. O'Garra Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus J. Immunol., July 15, 2005; 175(2): 1041 - 1046. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
