RNA-seq profiling of LPS tolerance in monocytes, THP-1, fibroblasts, smooth muscle cells, and endothelial cells

Atherosclerosis – a chronic disease of the arteries characterized by lipid accumulation and chronic local inflammation – is the primary cause of most ischemic cardiovascular diseases. The inflammatory process can be limited by endotoxin tolerance. This study performed a comparative transcriptomic analysis of LPS tolerance in primary monocytes, the THP-1 monocyte line, fibroblasts, endothelial cells, and smooth muscle cells. To model LPS tolerance, single and double LPS stimulation was performed. Sequencing of libraries obtained from total RNA after poly(A) selection was performed on the Illumina NextSeq 2000 platform. Primary monocytes and smooth muscle cells developed LPS tolerance; fibroblasts showed partial, mediator-dependent tolerance; THP-1 cells showed limited tolerance primarily for TNF; endothelial cells did not show tolerance for IL-8/CCL2. No conserved transcriptional tolerance signature was observed across tolerant cell types; overlap was limited to three genes (OAS1, IFIT2, IFIT3).