RIPK1 kinase-dependent gene expression in mouse microglia and astrocytes in vitro
To determine the role of RIPK1 kinase-dependent transcriptional signaling in microglia and astrocytes, we stimulated cells with RIPK1 kinase-activating stimuli TNF/5z-7 and TNF/Smac/zVAD in the presence or absence of the RIPK1 kinase inhibitor Nec-1s. We identified various genes modulated in a RIPK1 kinase-dependent manner with each stimulation in both microglia and astrocytes, and the main biological pathways were related to an inflammatory and immune response. We identified many cytokines and chemokines upregulated in both microglia and astrocytes upon RIPK1 kinase activation, demonstrating the contribution of RIPK1 kinase signaling to pro-inflammatory responses in microglia and astrocytes Overall design: 4 biological replicates of mouse microglia were treated with (1) DMSO, (2) Nec-1s, (3) TNF/5z-7, (4) TNF/Smac/zVAD, (5) TNF/5z-7/Nec-1s, and (6) TNF/Smac/zVAD/Nec-1s; 3 replicates of astrocytes were treated with (1) DMSO, (2) Nec-1s, (3) TNF/Smac/zVAD, (4) TNF/Smac/zVAD/Nec-1s