The Regulation of CCL19 Gene Expression in Human Antigen Presenting Cells (B49)

Abstract

Abstract CCL19 chemokine plays an important role in regulating DC traffic and recruitment of naïve T cells to the vicinity of activated DCs and macrophages. We have analyzed the regulation of CCL19 gene expression in human monocyte-derived DCs/macrophages infected with Salmonella enterica or Sendai virus. Computer analysis of the CCL19 promoter identified two putative NF-κB binding sites and one interferon stimulated response element (ISRE). Transcription factor binding experiments demonstrated that Salmonella or Sendai virus infection increased the binding of NF-κB proteins (p50, p52, p65, and RelB) to both CCL19 promoter NF-κB elements. Salmonella or Sendai virus infection also increased the binding of multiple IRFs, as well as STAT1 and STAT2, to the ISRE site. The role of NF-κB and various IRF family members in transcriptional control of CCL19 gene was further studied in transfection experiments. The expression of NF-κB dimers readily activated CCL19 promoter. The expression of IRF1, IRF3, or IRF7 proteins was also able to activate the promoter in the presence of Sendai virus infection. CCL19 promoter constructs containing mutated NF-κB and/or ISRE sites were weakly activated. Our data also suggests that c-Jun and c-Fos proteins binding to target AP-1 elements in CCL19 promoter plays a role in transcriptional control of CCL19. Further work focuses on the regulation of CCL19 in human macrophages and myeloid DCs.