Muscone Inhibits the Excessive Inflammatory Response in Myocardial Infarction by Targeting TREM-1

The inhibitory effect of muscone on the hyperinflammatory response after myocardial ischemia reperfusion injury (MIRI) was investigated, and the target and signal pathways of muscone were explored. The levels of inflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were detected through qRT-PCR and ELISA. The expression levels of p38 and NF-kappa B signaling pathway-related proteins were detected through Western blot. TREM-1 siRNA was transfected into macrophages in vitro. The rat model of myocardial ischemia was established and used in studying the inhibitory effect of muscone on the inflammatory response and its protective effect muscone on myocardial apoptosis. The expression of TREM-1 was upregulated during myocardial ischemia. Knocking down TREM-1 decreased the increase in inflammatory cytokines in the supernatant of macrophages induced by rmHMGB1 (1 mu g/mL) and rmHSP60 (1 mol/mL). In addition, knocking down TREM-1 decreased p38 and NF-kappa B signaling activation. Muscone can protect myocardial cells by inhibiting the expression of TREM-1 and the inflammatory response after myocardial infarction. Further study showed that muscone inhibited the production of DAM-triggered (damage-associated molecular pattern trigger) inflammatory cytokines. In addition, muscone inhibited the activation of p38 and NF-kappa B signals under DAM-induced conditions. Muscone and TREM-1 gene knockout reduced cell apoptosis and provided protection against MIRI by inhibiting p38 and NF-kappa B signaling activation. Mechanism studies showed that muscone inhibited the production and release of inflammatory cytokines by inhibiting TREM-1, and thereby reducing the inflammatory response and providing protection against MIRI.