Alogliptin inhibits IL-1β-induced inflammatory response in fibroblast-like synoviocytes.

Excessive production of pro-inflammatory cytokines such as interleukin (IL)-1β plays an important role in the chronic inflammation in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Alogliptin, an important selective dipeptidyl peptidase-4 (DPP-4) inhibitor licensed for the treatment of type 2 diabetes, has displayed a wide range of pharmacological capacities. In the present study, we aimed to investigate whether alogliptin possessed a protective effect against IL-1β-induced insult in FLS. Our results indicate that alogliptin treatment ameliorated IL-1β-induced production of reactive oxygen species, the expression of matrix metalloproteinase-3 (MMP-3) and MMP-13, secretions of tumor necrosis factor-α (TNF-α), IL-6, and IL-8. Additionally, we found that alogliptin inhibited c-Jun N-terminal kinase (JNK)/activator protein 1 (AP-1) signaling by reducing IL-1β-induced phosphorylation of JNK, the expression of c-Jun and c-Fos, and the luciferase activity of AP-1. Importantly, alogliptin suppressed IL-1β-induced activation of IκBα/NF-κB signaling by preventing the phosphorylation and degradation of IκBα, nuclear translocation of NF-κB p65, as well as the luciferase activity of AP-1. These findings suggest that alogliptin might have therapeutic potential for the treatment of chronic inflammation in RA.