Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice

Tornai, David; Furi, Istvan; Shen, Zu T.; Sigalov, Alexander B.; Coban, Sahin; Szabo, Gyongyi

To further assess the effects of the TREM-1 inhibitors on mechanisms of lipid metabolism, we tested genes involved in lipid synthesis (sterol regulatory element binding transcription factor 1 [SREBF1] and acetyl-coenzyme A carboxylase 1 [ACC1]) along with the lipid accumulation marker perilipin-2 (ADRP) (Fig. 5A-C) . Both TREM-1 inhibitors but not vehicle treatment prevented alcohol-induced up-regulation of SREBF1, ACC1, and ADRP at the mRNA level ( Fig. 5A-C) . To assess lipid oxidation, we tested peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase 1A (CPT1A), and medium-chain acyl-coenzyme A dehydrogenase (MCAD) mRNA levels in wholeliver samples (Fig. 5D-F) . Alcohol feeding significantly reduced mRNA expression of PPARα and CPT1A, while MCAD had a decreasing trend. Both TREM-1 inhibitors as well as the vehicle treatment significantly increased PPARα and MCAD levels compared to the untreated alcohol-fed controls (Fig. 5D-F) .