GSE109635
In human CD16+ monocytes NK1R signaling upregulates inflammatory pathways and negatively regulates apoptosis
The neurokinin-1 receptor (NK1R) pathway has immunomodulatory properties and is implicated in the pathophysiology of neurodegenerative, infectious and inflammatory diseases. Monocytes are important cells in inflammation and they consist of subsets with distinct phenotypes and biological functions. NK1R signaling is elevated in conditions that alter the balance of monocyte subsets, such as in HIV infection. In order to understand the pro-inflammatory mechanism of NK1R signaling in monocyte subsets, a transcriptome study was performed using RNA sequencing. Human primary peripheral monocytes were treated with the NK1R cognate ligand, substance P (SP), prior to being sorted into CD16- and CD16+ subsets. SP treatment led to the differential expression of 38 genes in CD16- monocytes and 12 genes in CD16+ monocytes. The canonical NF-?B pathway was activated in both subsets, as indicated by the upregulation of transcripts including IL1a, IL1ß, IL6, CCL3 and CCL4. In the CD16+ monocytes, NK1R signaling led to priming of the NLRP3 inflammasome and upregulated transcripts including NLRP3 and CARD16. Alternative splicing analysis showed that NK1R signaling resulted in differential exon usage of CASP1 and CARD16 in CD16+ monocytes. SP treatment altered the properties of both CD16- and CD16+ monocytes, leading to an inflammatory response with activation of the canonical NF-?B pathway in both monocyte subsets, and priming of the NLRP3 inflammasome in the CD16+ subset. Overall design: mRNA transcript analysis of primary human CD16- and CD16+ monocyte subsets under no treatment conditions (3 replicates), SP treatment  (2 replicates) or treatment with vehicle control (2 replicates) using the Illumina HiSeq 4000 Sequencing System mRNA transcript analysis of primary human CD16- and CD16+ monocyte subsets under SP treatment  (6 replicates) or treatment with vehicle control (6 replicates) using the Illumina NovaSeq 6000 Sequencing System