Multiple NF-kappaB and IFN regulatory factor family transcription factors regulate CCL19 gene expression in human monocyte-derived dendritic cells.
CCL19 chemokine has a central role in dendritic cell (DC) biology regulating DC traffic and recruitment of naive T cells to the vicinity of activated DCs. In this study, we have analyzed the regulation of CCL19 gene expression in human monocyte-derived DCs. DCs infected with Salmonella enterica or Sendai virus produced CCL19 at late times of infection. The CCL19 promoter was identified as having two putative NF-kappaB binding sites and one IFN-stimulated response element (ISRE). Transcription factor binding experiments demonstrated that Salmonella or Sendai virus infection increased the binding of classical p50+p65 and alternative p52+RelB NF-kappaB proteins to both of the CCL19 promoter NF-kappaB elements. Interestingly, Salmonella or Sendai virus infection also increased the binding of multiple IFN regulatory factors (IRFs), STAT1, and STAT2, to the ISRE element. Enhanced binding of IRF1, IRF3, IRF7, and IRF9 to the CCL19 promoter ISRE site was detected in Salmonella or Sendai virus-infected cell extracts. The CCL19 promoter in a luciferase reporter construct was activated by the expression of NF-kappaB p50+p65 or p52+RelB dimers. IRF1, IRF3, and IRF7 proteins also activated CCL19 promoter in the presence of Sendai virus infection. CCL19 promoter constructs mutated at NF-kappaB and/or ISRE sites were only weakly activated. Ectopic expression of RIG-I (DeltaRIG-I, CARDIF) or TLR3/4 (TRIF, MyD88, IKKepsilon, or TBK1) signaling pathway components induced CCL19 promoter activity, suggesting that these pathways are important in CCL19 gene expression. Our experiments reveal that expression of the CCL19 gene is regulated by a combined action of several members of the NF-kappaB, IRF, and STAT family transcription factors.
Pietilä
Taija E
TE
Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland. taija.pietila@ktl.fi
Veckman
Ville
V
Lehtonen
Anne
A
Lin
Rongtuan
R
Hiscott
John
J
Julkunen
Ilkka
I
D001483:Base Sequence; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic; D020218:Response Elements; D019779:Salmonella enterica / Q000276:immunology; D029082:Sendai virus / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
C515460:CCL19 protein, human; C108355:CCL20 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D050835:Interferon Regulatory Factors; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D014157:Transcription Factors; D007371:Interferon-gamma; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases