miR-135b-5p inhibits LPS-induced TNFβ production via silencing AMPK phosphatase Ppm1e

AMPK activation in monocytes could suppress lipopolysaccharide (LPS)induced tissue-damaging TNF beta production. We are set to provoke AMPK activation via microRNA ("miRNA") downregulating its phosphatase Ppm1e. In human U937 and THP-1 monocytes, forced expression of microRNA-135b-5p ("miR-135b-5p") downregulated Ppm1e and activated AMPK signaling. Further, LPS-induced TNF alpha production in above cells was dramatically attenuated. Ppm1e shRNA knockdown in U937 cells also activated AMPK and inhibited TNF alpha production by LPS. AMPK activation is required for miR-135b-induced actions in monocytes, AMPK alpha shRNA knockdown or T172A dominant negative mutation almost abolished miR-135b-5p's suppression on LPS-induced TNF alpha production. Significantly, miR-135b-5p inhibited LPS-induced reactive oxygen species (ROS) production, NF kappa B activation and TNF alpha mRNA expression in human macrophages. AMPK alpha knockdown or mutation again abolished above actions by miR-135b-5p. We conclude that miR-135b-5p expression downregulates Ppm1e to activate AMPK signaling, which inhibits LPS-induced TNFa production via suppressing ROS production and NF kappa B activation.