CXC chemokine receptor 3 antagonist AMG487 shows potent anti-arthritic effects on collagen-induced arthritis by modifying B cell inflammatory profile.

CXC chemokine receptor 3 antagonist AMG487 shows potent anti-arthritic effects on collagen-induced arthritis by modifying B cell inflammatory profile. Immunol Lett. 2020 Jun 23;: Authors: Bakheet SA, Alrwashied BS, Ansari MA, Nadeem A, Attia SM, Alanazi MM, Aldossari AA, Assiri MA, Mahmood HM, Al-Mazroua HA, Ahmad SF Abstract Several studies have suggested that chemokine receptors are important mediators of inflammatory response in rheumatoid arthritis (RA). B cells are also known to play an important role in RA pathology. C-X-C chemokine receptor type 3 (CXCR3) is considered a potential therapeutic target in different inflammatory diseases; however, the mechanism remains unclear. Here, we evaluated the potentially protective effect of AMG487, a selective CXCR3 antagonist, in collagen-induced arthritis (CIA) mouse model. CIA mice were treated with AMG487 (5 mg/kg) every 48 h, from day 21 until day 41. We then investigated the effect of AMG487 on NF-κB p65-, NOS2-, MCP-1-, TNF-α-, IFN-γ, IL-4-, and IL-27-producing CD19+ B cells in the spleen through flow cytometry. We also evaluated the mRNA and protein expression levels of these molecules using RT-PCR and western blotting in the knee tissues. Our results revealed that AMG487-treated mice showed decreased NF-κB p65-, NOS2-, MCP-1-, and TNF-α-, and increased IL-4-, and IL-27-producing CD19+ B cells compared with the control mice. Additionally, AMG487 treatment significantly do...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research