The cysteinyl leukotriene receptor 1 (CysLT1R) antagonist montelukast suppresses matrix metalloproteinase-13 expression induced by lipopolysaccharide

• Published in: International immunopharmacology 2018-02, Vol.55, p.193-197
• Main Authors: Wei, Jinsong, Chen, Siyuan, Huang, Chengshuo, Guo, Weixiong, Yang, Shukai, Feng, Bailin, Chu, Jiaqi
• Format: Article
• Language: English
• Subjects: Acetates; Animals; Antagonist drugs; Anti-Asthmatic Agents; Asthma; Biocompatibility; Biodegradation; Biomedical materials; Bone diseases; Bone Diseases - drug therapy; Bone matrix; Cell Line; Collagen; Collagenase 3; Degradation; Extracellular matrix; Fibrils; Gene Expression Regulation; Humans; Leukocytes (eosinophilic); Leukotrienes; Lipopolysaccharides; Lipopolysaccharides - metabolism; LPS; Matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Metalloproteinase; Mice; MMP-13; Montelukast; NF-kappa B - metabolism; NF-κB protein; Nuclear transport; Osteoblast; Osteoblasts; Osteoblasts - drug effects; Osteoblasts - physiology; Pharmacology; Phosphorylation; Proteolysis; Quinolines; Receptors, Leukotriene - metabolism; RNA, Small Interfering - genetics; Suppressor of Cytokine Signaling 3 Protein - genetics; Suppressor of Cytokine Signaling 3 Protein - metabolism; Time dependence; Transcription; Translocation
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.11.020

Bacterial products such as LPS are critical factors responsible for bone destruction. MMP-13, a member of the matrix metalloproteinase family, plays a critical role in the proteolytic degradation of extracellular matrix components, which includes collagen fibrils in the bone matrix. Montelukast is a selective cysteinyl leukotrienes receptor 1 (cysLT1R) antagonist used clinically for the treatment of asthma, as it reduces eosinophilic inflammation in airways. This study aims to explore the role of montelukast in regulating MMP-13 expression induced by LPS in osteoblasts. Our results indicate that LPS stimulated cysLT1R expression in mouse MC3T3-E1 osteoblasts in a dose- and time-dependent manner. Notably, LPS-induced up-regulation of MMP-13 was ameliorated by treatment with montelukast in a dose-dependent manner. Furthermore, treatment with montelukast stimulated the expression of SOCS3, an inhibitor of MMP-13. Silencing of SOCS3 abolished the inhibitory effects of montelukast on MMP-13 expression. Mechanistically, we found that montelukast suppressed LPS-induced nuclear translocation of NF-κB p65 as well as NF-κB transcriptional activity by inhibiting the phosphorylation and degradation of IκBα. These data suggest that montelukast can modulate inflammatory events in bone diseases. •cysLT1R is increased by LPS in a dose and time dependent manner in MC3TC-E1 cells.•Montelukast attenuated LPS-induced up-regulation of MMP-13 in MC3TC-E1 cells.•Montelukast ameliorated LPS-induced reduction of SOCS-3 in MC3TC-E1 cells.•Montelukast ameliorated LPS-induced activation of IκBα and NF-κB.