Quetiapine Ameliorates Collagen-induced Arthritis in Mice Via the Suppression of the AKT and ERK Signaling Pathways

Overview

Journal Inflamm Res

Specialties Allergy & Immunology
Pathology

Date 2018 Aug 16

PMID 30109356

Citations 5

Authors

Yi-Ju Pan

Wei-Hsun Wang

Tzu-Yao Huang

Wei-Hsiang Weng

Chun-Kai Fang

Yu-Chan Chen

Jeng-Jong Hwang

Affiliations

Soon will be listed here.

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. F-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 F-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 F-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.

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