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

In addition to attenuating inflammatory processes, the TREM-1 inhibitory formulations also ameliorated hepatocyte damage and steatosis. Serum ALT and liver triglyceride levels were both decreased in the GF9-HDL, GA/E31-HDL, and HDL-vehicle treated groups. The vehicle also had an inhibitory effect on TNF-α and MCP-1 protein levels as well as on mRNA expression of neutrophil and fibrosis markers, indicating that the HDL vehicle formulation can attenuate inflammation to a moderate extent. A previous study found evidence that HDL can protect hepatocytes from endoplasmic reticulum stress, (41) while other publications reported a scavenger function of HDL for LPS and lipoteichoic acid (42, 43) that could prevent immune cells from being activated by those molecules. (42, 43) Further, the observed moderate beneficial effect of HDL treatment alone on fatty acid oxidation markers in alcohol-exposed mice ( Fig. 5A -C) is in line with data that demonstrate infusion of reconstituted HDL reduces fatty acid oxidation in patients with type 2 diabetes mellitus. (44) In human and rat plasma, apo A-I, the major protein of HDL, has been shown to inhibit lipid peroxidation. (45) These data might provide an explanation for our findings of the hepatoprotective effects of HDL.