RGS10 differentially modulates NFκB subunit transcription and inflammatory cytokine profiles in peritoneal macrophages

Abstract Regulator of G-protein signaling 10 (RGS10) has been shown to regulate multiple inflammatory pathways relevant to disease pathogenesis. Of particular importance is the ability of RGS10 to negatively regulate the NFkB pathway, a prominent pro-inflammatory pathway implicated in multiple inflammatory disease phenotypes. However, the exact mechanism by which RGS10 regulates NFkB is unknown. Considering that RGS10 translocates into the nucleus upon stimulation, we hypothesize that RGS10 may regulate NFKB through transcription. To determine whether RGS10 mediates NFkB transcription, we stimulated RGS10 KO and B6 peritoneal macrophages and collected cell lysate over 24 hours to assess transcript levels of NFkB and related proinflammatory cytokines. Here we found that RGS10 differentially regulates the transcription of NκKB subunits and NFκB-dependent cytokines. Further studies are warranted to understand the potential role of RGS10 in transcriptional regulation of inflammatory states. Competing Interest Statement The authors have declared no competing interest. Footnotes This version of the manuscript has been revised to update the title. Abbreviations - BME - Beta mercaptoethanol - cDNA - complementary DNA - Cox2 - Cyclooxygenase 2 - DNA - Deoxyribonucleic Acid - DPBS - Dulbecco’s Phosphate Buffered Saline - GPCR - G Protein Coupled Receptor - IL-12 - Interleukin 12 - IL-12p40 - Interleukin 12p40 - IL-1β - Interleukin 1β - KCGRO - Keratinocyte chemoattractant/Growth-regulated oncogene - KO - Knock Out - LLOD - Lower limit of detection - LPS - Lipopolysaccharide - MSD - Mesoscale Discovery - NFkB - Nuclear Factor kappa-light-chain-enhancer of activated B cells - pMac - Peritoneal macrophages - QPCR - Quantitative real time polymerase chain reaction - RA - Rheumatoid Arthritis - RGS10 - Regulator of G Protein Signaling 10 - RNA - Ribonucleic Acid - RPMI 1640 - Roswell Park Memorial Institute 1640 - STIM2 - Stromal interaction molecule 2 - TNF - Tumor Necrosis Factor - WT - Wild type