Distinct regulation of gene promoters and enhancers by CXCL4 and TLR8 in human CD14+ monocytes. Distinct regulation of gene promoters and enhancers by CXCL4 and TLR8 in human CD14+ monocytes

To gain a comprehensive understanding of gene regulation in CXCL4 and TLR8 signaling crosstalk, we treated primary human blood monocytes with CXCL4 and TLR8 ssRNA ligand ORN8L for 6 h and performed transcriptomic analysis via RNA-seq. We observed that CXCL4 interacted with TLR8 ssRNA ligand and triggered inflammatory cytokine storm including IL6, IL12p40, TNF and IFNβ, and pro-fibrotic gene expression and activated NLRP3 inflammasome leading to interleukin-1β (IL-1β) secretion and pyroptosis in human blood monocytes. Overall design: Examination of open chromatin regions by ATAC-seq in human CD14+ monocytes exposed for 6 h to CXCL4 ( 10 ug/ml) or ORN8L( 20 ug/ml) or both CXCL4 and ORN8L