Yi-Ju Pan1,2, Wei-Hsun Wang3,4, Tzu-Yao Huang5, Wei-Hsiang Weng5, Chun-Kai Fang6, Yu-Chan Chen7, Jeng-Jong Hwang8,9. 1. Department of Psychiatry, Far Eastern Memorial Hospital, Banciao, New Taipei City, 220, Taiwan. 2. School of Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan. 4. Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kao-hsiung, Taiwan. 5. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. 6. Department of Psychiatry and Suicide Prevention Center, Mackay Memorial Hospital, No. 155, Sec.2, Li-Nong Street, Bei-tou, Taipei, 112, Taiwan. 7. Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan. 8. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. jjhwang@ym.edu.tw. 9. Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan. jjhwang@ym.edu.tw.
Abstract
OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice. TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1β were decreased, while immunosuppressive factors such as TGF-β and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of 18F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.
OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice. TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1β were decreased, while immunosuppressive factors such as TGF-β and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of 18F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.
Authors: Jacqueline M Benson; Clifford W Sachs; George Treacy; Honghui Zhou; Charles E Pendley; Carrie M Brodmerkel; Gopi Shankar; Mary A Mascelli Journal: Nat Biotechnol Date: 2011-07 Impact factor: 54.908
Authors: George Mihai Nitulescu; Maryna Van De Venter; Georgiana Nitulescu; Anca Ungurianu; Petras Juzenas; Qian Peng; Octavian Tudorel Olaru; Daniela Grădinaru; Aristides Tsatsakis; Dimitris Tsoukalas; Demetrios A Spandidos; Denisa Margina Journal: Int J Oncol Date: 2018-10-16 Impact factor: 5.650