Knockdown of triggering receptor expressed on myeloid cells1 (TREM1) inhibits endoplasmic reticulum stress and reduces extracellular matrix degradation and the apoptosis of human nucleus pulposus cells.

Abstract

According to the linear model of microarray data analysis, triggering receptor expressed on myeloid cells 1 (TREM1) has been shown to have a significantly different expression profile between intervertebral disc degeneration (IDD) samples and associated control samples. The purpose of the present study was to explore the probable role and underlying mechanism of TREM1 in IDD. To accomplish this, an in vitro model of IDD was established by using IL-1β to stimulate human nucleus pulposus cells (NPCs). After the level of TREM1 had been determined, its functions in terms of the viability of the NPCs, extracellular matrix (ECM) degradation, inflammation, apoptosis and endoplasmic reticulum stress (ERS) were assessed. The downstream target of TREM1 was predicted to be Toll-like receptor-4 (TLR-4) and its roles were then studied, incorporating experiments featuring an ERS agonist. IL-1β was found to elevate the level of TREM1 in NPCs. TREM1 knockdown reversed the observed effects of IL-1β on cell viability, ECM degradation, inflammation, apoptosis of NPCs, ERS and TLR4/NF-κB signaling. Subsequently, the TLR4 and ERS agonists were found to reverse the effect of TREM1 knockdown on NPCs, indicating that the TLR4/NF-κB signaling pathway and ERS were responsible for mediating the regulation of TREM1. In conclusion, the present study showed that TREM1 knockdown blocked the TLR4/NF-κB signaling pathway, inhibited ERS and reduced the levels of ECM degradation and apoptosis of NPCs induced by IL-1β.