MDAs including MMAE enhanced the cGAMP-mediated STING pathway.

Abstract

(A, B, E, and G) THP1-Lucia ISG (WT and STING KO) and RAW-Lucia ISG cells were treated with 2’3’-cGAMP (cGAMP, 0.5 μM) and/or indicated doses of MDAs or MMAE for 24 h, and the fold change of luminescence was normalized to DMSO or cGAMP-treated cells. (C, D, F, and H) THP1-Lucia ISG (WT and STING KO) and MEF cells were treated with cGAMP (0.5 μM) and/or indicated concentrations of MMAE for indicated times (C, D and F) or 6 h (H), and activation of the STING pathway were analyzed by immunoblotting. (I-L) THP1-Lucia ISG cells (WT and STING KO) and BMDMs (WT, Stinggt/gt, or Myd88-/- mice) were stimulated with cGAMP and/or indicated concentrations of MMAE for 12 h (I, K) or 6 h (J, L). IFNβ production was measured by ELISA analysis (I and K). the activation of STING pathway was analyzed by immunoblotting (J). mRNA expression levels of IFNβ, CCL5 and CXCL10 in BMDMs (WT, Stinggt/gt, or Myd88-/- mice) (n = 3 biological replicates) (L). cGAMP was used at 0.5 μM for all experiments unless otherwise noted.</p