Journal: JCI Insight

Article Title: Innate immune activation and mitochondrial ROS induce acute and persistent cardiac conduction system dysfunction after COVID-19

doi: 10.1172/jci.insight.193164

Figure Lengend Snippet: ( A ) Schematic of molecular mechanisms of COVID-19 and dsRNA induced IFN response. Ruxolitinib suppresses IFN-stimulated response and mitoTEMPO suppresses mitochondrial damage and oxidative stress. (Created with BioRender.com.) ( B and C ) Inhibition of JAK/STAT signaling with ruxolitinib (Rux) (1 μM) significantly suppressed PIC-mediated induction of the interferon response signaling proteins STAT1, p-STAT1, IRF9, and MX1 in hiPSC-CM monolayers. MitoTEMPO (MT) (1 μM) does not significantly suppress the IFN response. Bar graphs show relative band intensity normalized to total protein loading (1-way ANOVA with Tukey’s multiple-comparison test). Lysates were from 3–5 different hiPSC-CM samples. ( C ) Inhibition of JAK/STAT signaling in hiPSC-derived engineered heart tissues (EHTs) with ruxolitinib, but not mitoTEMPO (MT), decreased the interferon response of signaling proteins STAT1, pSTAT1, IRF9, and MX1. Lysates loaded for the Western blot in C were from 3 different EHTs. ( D ) Cytokine secretion into the media induced by PIC, measured using a human Proteome Profiler array (inset shows exemplar blots), was greatly suppressed by Rux treatment in hiPSC-CM.

Article Snippet: Using a human cytokine antibody array (Proteome Profiler, R&D Systems), we found that PIC induced the secretion of a plethora of cytokines into the media from hiPSC-CM, including a >2-fold increase in 36 of the 105 cytokines assayed ( and ).

Techniques: Inhibition, Comparison, Derivative Assay, Western Blot