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

Neutrophil infiltration of the liver is a characteristic of alcoholic hepatitis; therefore, we investigated markers associated with this cell population. Expression of the neutrophil markers Ly6G and MPO were significantly increased in livers of alcohol-fed mice compared to PF controls. This was fully prevented by TREM-1 blockade (Fig. 3E,F) . Interestingly, the HDL vehicle alone also resulted in a decreasing trend of Ly6G and MPO expression in alcohol-fed mice; however, the GF9-HDL and GA/E31-HDL TREM-1 inhibitors significantly attenuated Ly6G and MPO levels even when compared to the vehicle-treated alcohol-fed mice (Fig. 3E,F) . MPO staining on IHC confirmed that both TREM-1 inhibitors significantly reduced MPO-positive cell numbers compared to the untreated alcohol-fed control group (Fig. 3G,H) .