Fig. 2. Pharmacologic inhibition of ALK impairs STING activation.

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Fig. 2. Pharmacologic inhibition of ALK impairs STING activation. Pharmacologic inhibition of ALK impairs STING activation. (A) iBMDMs were stimulated with indicated STING ligands (10 μg/ml) in the absence or presence of LDK378 (10 μM), AP26113 (10 μM), or control vehicle [dimethyl sulfoxide (DMSO)] for 16 hours, and the release of IFNβ was assayed using ELISA (n = 3; data are means ± SD; *P < 0.05 versus DMSO group, ANOVA LSD test). (B) Heatmap of IFNβ release changes in macrophages or monocytes after STING ligand (10 μg/ml) stimulation in combination with LDK378 (10 μM), AP26113 (10 μM), or vehicle (DMSO) for 16 hours. (C) iBMDMs were stimulated with indicated STING ligands (10 μg/ml) in the absence or presence of LDK378 (10 μM), AP26113 (10 μM), or vehicle (DMSO) for 16 hours, and IFNβ mRNA was assayed with quantitative polymerase chain reaction (n = 3; data are means ± SD; *P < 0.05 versus DMSO group, ANOVA LSD test). (D) Heatmap of IFNβ mRNA changes in macrophages or monocytes after STING ligand (10 μg/ml) stimulation in combination with LDK378 (10 μM), AP26113 (10 μM), or vehicle (DMSO) for 16 hours. AU, arbitrary units. (E and F) Western blot analysis of indicated protein expression in iBMDMs (E) or J774A.1 cells (F) after 3′3′-cGAMP (10 μg/ml) stimulation in combination with LDK378 (10 μM), AP26113 (10 μM), or vehicle (DMSO) for 3 to 16 hours. (G and H) Western blot analysis of indicated protein expression in iBMDMs (G) or J774A.1 cells (H) after c-di-AMP (10 μg/ml) or DMXAA (10 μg/ml) stimulation in combination with LDK378 (10 μM), AP26113 (10 μM), or vehicle (DMSO) for 16 hours. Ling Zeng et al., Sci Transl Med 2017;9:eaan5689 Published by AAAS