Figure 3

Inhibition of cytokine production by MEK and ERK inhibitors. (A) Cytokine expression in macrophages differentiated from THP1 cells upon exposure to LPS, with or without glucocorticoids (dexamethasone and hydrocortisone), MEK inhibitors (trametinib and selumetinib) and an ERK inhibitor (SCH-772984). IL-6 and IL-1β levels were measured by ELISA (pg/ml), and TNF-α by qPCR (2^−ΔΔCt (FC)). The experiment was repeated three times and a representative example is shown. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 (t test). (B) GSEA analysis from human bronquial cells treated with trametinib or DMSO as a control. Differential expression analyses were done from data publicly available at GEO (GSE63229). Pathways names together with their gene ranks, Normalized Enrichment Scores (NES), p-values (pval) and adjusted p-values (padj) are shown. (C) Enrichment plot of genes belonging to the “Inflammatory response” pathway resulting from the GSEA analysis mentioned in (B) illustrating the inhibition of their expression levels by trametinib in human bronchial cells. (D) GSEA analysis from human monocytes treated with trametinib or DMSO as a control. Differential expression analyses were done from data publicly available at GEO (GSE123574). Pathways names together with their gene ranks, Normalized Enrichment Scores (NES), p-values (pval) and adjusted p-values (padj) are shown. (E) Enrichment plot of genes belonging to the “Inflammatory response” pathway resulting from the GSEA analysis mentioned in (D) illustrating the inhibition of their expression levels by trametinib in human monocytes.