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

Our study shows that TREM-1 inhibitors with HDL formulation exerted significant inhibition on early signaling events of proinflammatory processes at the level of cytokine mRNA and the activated p-SYK protein levels compared to the HDL vehicle alone in a mouse model of ALD. This effect presumably would be even more obvious at the protein level of cytokines in a more severe liver injury. However, in mice, the most commonly used 5-week alcohol feeding that we used resulted in moderate liver damage and minimal inflammation, (25) which is a limitation of our study. Importantly, as shown on the stained liver sections, the GF9-HDL and GA/ E31-HDL formulations significantly inhibited immune cell infiltration and steatosis compared to the HDL vehicle only group [Correction made 31 October, 2018. The word group was added.] in mice with ALD. Thus, exploration of TREM-1 inhibitors in decreasing inflammation deserves further investigation in ALD.