montelukast and Synovitis

Montelukast, a potent selective antagonist of cysteinyl leukotriene (cysLT) receptors, has displayed its important anti-oxidative and anti-inflammatory effects in various tissues and organs. Rheumatoid arthritis (RA) is an immune disease defined by hyperplastic synovitis and joint destruction. Fibroblast-like synoviocytes in RA (RA-FLSs) are the main cell component of the hyperplastic synovium. Whether montelukast can protect against the inflammatory milieu of RA remains unclear. Here, it is shown that cysLT1R is present in FLSs and unregulated in RA-FLSs. Montelukast has an inhibitory effect on the inflammatory microenvironment of RA by decreasing the secretion of IL-6, IL-8, MMP-3 and MMP-13 in FLSs induced by IL-1β. Notably, treatment with montelukast attenuated IL-1β-induced phosphorylation of IκBα, IκBα degradation, nuclear translocation of p65 and NF-κB activity to express a luciferase reporter gene in FLSs. The findings of the current study provide evidence for a novel therapeutic strategy for RA using montelukast.

Topics: Acetates; Arthritis, Rheumatoid; Cells, Cultured; Cellular Microenvironment; Cyclopropanes; Cytokines; Fibroblasts; Humans; I-kappa B Kinase; Inflammation Mediators; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; NF-kappa B; Phosphorylation; Quinolines; Receptors, Leukotriene; Signal Transduction; Sulfides; Synoviocytes; Synovitis