Fig. 5: Myristic acid inhibits cGAS-STING activation via facilitating N-myristoylation. | Nature Communications

Fig. 5: Myristic acid inhibits cGAS-STING activation via facilitating N-myristoylation.

From: Myristic acid as a checkpoint to regulate STING-dependent autophagy and interferon responses by promoting N-myristoylation

Fig. 5

a–c Quantitative polymerase chain reaction (qPCR) analysis of Ifnb1 mRNA in peritoneal macrophages (PMs) pretreated with DMSO, 2-HOM, DDD85646, or IMP-1088, following HSV-1 infection, cGAMP or 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulation, n = 3 samples examined over 3 independent experiments. d Luciferase activity analysis of interferon (IFN)-β activation in HEK293-Dual hSTING-A162 cells pretreated with DMSO, 2-HOM, or DDD85646, followed by DMXAA stimulation, n = 3 samples examined over 3 independent experiments. e Immunoblot analysis of p-TBK1 and p-IRF3 in PMs pretreated with DMSO or DDD85646, and then stimulated with DMXAA. f, g qPCR analysis Ifnb1 mRNA expression (f) or enzyme-linked immunosorbent assay (ELISA) (h) analysis of IFN-β secretion in PMs pretreated with DDD85646, and then treated with myristic acid, followed by ISD stimulation, n = 3 samples examined over 3 independent experiments. h qPCR analysis of Ifnb1 mRNA in PMs pretreated with IMP-1088, and then treated with myristic acid, followed by DMXAA stimulation, n = 3 samples examined over 3 independent experiments. i Immunoblot analysis of indicated proteins in PMs pretreated with DDD85646, and then treated with myristic acid, followed by HSV-1 infection. j Immunoblot analysis of LC3 in PMs from Sting or Sting mice pretreated with DDD85646, followed by cGAMP stimulation. k, l C57BL/6J mice were orally administered with DDD85646 and then infected with HSV-1 (2 × 10+/+-/-7 p.f.u. per mouse) by intraperitoneal injection. Serum levels of IFN-β, IL-6, and TFN-α were analyzed by ELISA (PBS group, n = 2; mock HSV-1 group, n = 4) (k). qPCR analysis of HSV-1 UL30 mRNA level in lung, brain, and spleen (PBS group, n = 2; mock HSV-1 group, n = 6) (l). Statistical significance was determined by unpaired two-sided multiple Student’s t-tests in (a–d), (f–h), and (k, l). Data are shown as mean ± standard deviation (SD) or typical photographs and are representative of three biological independent experiments with similar results. *P < 0.05, **P < 0.01, ***P < 0.001. Source data is provided in the Source data file.

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