Expression of TREM-2 and its inhibitory effects on TNF-α induced inflammation in fibroblast-like synoviocytes via inhibiting p38 pathway activation.

OBJECTIVES: It is not clear whether TREM-2 (the "triggering receptor expressed on myeloid cells 2") is expressed in fibroblast-like synovial cells (FLSs). In this study, we aimed to determine the expression of TREM-2 in rheumatoid arthritis (RA)-FLSs and explore whether and how TREM-2 modulates the function of RA-FLSs. METHODS: Western blot and RT-PCR were used to detect the expression of TREM-2 in RA-FLSs, siRNA and lentivirus were used to down-regulate and up-regulate the expression of TREM-2 in RA-FLSs. Then mRNA expression of IL-1ß, IL-6, and MMP-13 was determined by RT-qPCR. Protein secretion of IL-1ß, IL-6, and MMP-13 in the supernatant was determined by ELISA assay; expression of cell signal transduction molecules was determined by western blot. RESULTS: A: Relative to OA-FLSs, mRNA and protein expression levels of TREM-2 in RA-FLSs are significantly elevated. TREM-2 protein is mainly expressed in the cytoplasm of RA-FLSs; B: In RA, the expression of TREM-2 was reduced at first and then up-regulated after stimulation by TNF-α. TREM-2 also inhibited the activation of TNF-α induced of inflammation in RA-FLSs by the p38 pathway, which regulates the production of cytokines and matrix metalloproteinases. CONCLUSIONS: TREM-2 expressed in RA-FLSs and TNF-α mediated reduction of inflammatory reactions. These phenomena indicated that TREM-2 may be a potential target in the treatment of RA.

Regulation of human mesenchymal stem cell differentiation by TREM-2.

Activation of the triggering receptor expressed on myeloid cells 2 (TREM-2) regulates myeloid cell function in vitro. However, the failure to detect TREM-2 protein expression in vivo has hampered studies on immunological and other physiological TREM-2 functions. This study demonstrates that TREM-2 is expressed by human mesenchymal stem cells (h-MSCs) and responds to the toll-like receptor (TLR) ligand lipopolysaccharide (LPS). Knockdown of TREM-2 in h-MSCs using a small interfering RNA (siRNA) reduced the expression levels of TLR2, TLR4, and TLR6, inhibited osteogenic, chondrogenic, and adipogenic differentiation under specific induction conditions, and enhanced LPS-evoked inflammatory cytokine production. Thus, activation of TREM-2 may restrain h-MSC immune activation and promote differentiation for tissue repair.