Sheng Hui Huang1, Gui Wang Liu2, Jian Hua Li3, Jin Huang Xu4, Da Wei Xu5, Wei Qiong Zhang4, Jian Rong Huang6. 1. Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou; Department of Orthopaedics, the Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China. 2. Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou; Department of Orthopaedics and Traumatology, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Guangdong, China. 3. Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangdong, China. 4. Department of Orthopaedics, Zengcheng District People's Hospital, Guangzhou, China. 5. Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 6. Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou; Department of Orthopaedics, Zengcheng District People's Hospital, Guangzhou, China. guke16@163.com.
Abstract
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-1β, IL-6, and MMP-13 was determined by RT-qPCR. Protein secretion of IL-1β, 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.
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-1β, IL-6, and MMP-13 was determined by RT-qPCR. Protein secretion of IL-1β, 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.
Authors: Zoe M Tapp; Julia E Kumar; Kristina G Witcher; Ravitej R Atluri; John A Velasquez; Shane M O'Neil; Julia E Dziabis; Chelsea E Bray; John F Sheridan; Jonathan P Godbout; Olga N Kokiko-Cochran Journal: J Neurotrauma Date: 2020-04-21 Impact factor: 5.269