Seung Min Jung1, Jaeseon Lee2, Seung Ye Baek2, Juhyun Lee2, Se Gwang Jang2, Seung-Min Hong2, Jin-Sil Park2, Mi-La Cho2, Sung-Hwan Park3, Seung-Ki Kwok4. 1. Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 3. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 4. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: seungki73@catholic.ac.kr.
Abstract
OBJECTIVES: Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. METHODS: Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro. The effects of EP on osteoclastogenesis were determined by staining for tartrate-resistant acid phosphatase, and measuring the mRNA levels of osteoclastogenesis-related genes. The expression of high-mobility group box 1 (HMGB1) was evaluated after EP therapy using immunohistochemical staining and Western blotting. RESULTS: EP significantly improved the clinical and histological features of arthritis in CIA mice. EP suppressed the differentiation of CD4+ T cells into Th17 cells, and inhibited the expression of RORγt. The generation of osteoclasts and osteoclastogenic markers from murine and human monocytes was significantly reduced in the presence of EP. The expression of HMGB1 in the synovium was significantly lower in CIA mice treated with EP, compared to control CIA mice. During osteoclastogenesis, HMGB1 release from monocytes was inhibited in the presence of EP. CONCLUSIONS: EP attenuated synovial inflammation and bone destruction in the experimental arthritis model through suppression of IL-17 and HMGB-1. The data suggests that EP could be a novel therapeutic agent for the treatment of inflammatory arthritis, such as rheumatoid arthritis.
OBJECTIVES:Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. METHODS:Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro. The effects of EP on osteoclastogenesis were determined by staining for tartrate-resistant acid phosphatase, and measuring the mRNA levels of osteoclastogenesis-related genes. The expression of high-mobility group box 1 (HMGB1) was evaluated after EP therapy using immunohistochemical staining and Western blotting. RESULTS:EP significantly improved the clinical and histological features of arthritis in CIA mice. EP suppressed the differentiation of CD4+ T cells into Th17 cells, and inhibited the expression of RORγt. The generation of osteoclasts and osteoclastogenic markers from murine and human monocytes was significantly reduced in the presence of EP. The expression of HMGB1 in the synovium was significantly lower in CIA mice treated with EP, compared to control CIA mice. During osteoclastogenesis, HMGB1 release from monocytes was inhibited in the presence of EP. CONCLUSIONS:EP attenuated synovial inflammation and bone destruction in the experimental arthritis model through suppression of IL-17 and HMGB-1. The data suggests that EP could be a novel therapeutic agent for the treatment of inflammatory arthritis, such as rheumatoid arthritis.
Authors: Ni Zhang; Hui Zhang; Betty Yuen Kwan Law; Ivo Ricardo De Seabra Rodrigues Dias; Cong Ling Qiu; Wu Zeng; Hu Dan Pan; Jin Yun Chen; Yan Fu Bai; Jing Lv; Li Qun Qu; Xi Chen; Qi Huang; Wei Zhang; Li Jun Yang; Lu Yu; Yu Han; Guo Xin Huang; Hui Miao Wang; Xiao Lei Sun; Yun Zhang; Hu Qiang He; Wei Dan Luo; Yao Xiao; Jian Zhou; Ting Xu; Qing Chun Huang; Min Wu; Zhi Sheng Huang; Wei Liu; Vincent Kam Wai Wong; Liang Liu Journal: Cell Mol Immunol Date: 2020-02-25 Impact factor: 11.530