The expression of Kruppel-like factor 2 in mice with collagen-induced arthritis and its role in the induction of nitric oxide synthase production

Abstract

Kruppel-like factor 2 (KLF2) is associated with acute and chronic inflammation. However, the role of KLF2 in rheumatoid arthritis (RA) remains unknown. Here, we investigated the expression of KLF2 in mice with collagen-induced arthritis (CIA) to determine whether KLF2 levels correlate with inducible nitric oxide synthase (iNOS) production in vitro. Hematoxylin and eosin staining was used to assess the synovitis and bone destruction in mice. The concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and nitric oxide (NO) in synovial fluid was determined by enzyme-linked immunosorbent assay, while western blot (WB) analysis was employed to detect the expression of KLF2 and iNOS in the synovium, heart, and kidneys. The expression of iNOS in MH7A cells was analyzed by quantitative polymerase chain reaction (PCR) and WB. The expression of KLF2 and iNOS was significantly elevated in the synovium, heart, and kidneys of CIA mice. This was correlated to an increase in the severity of arthritis and the concentration of inflammatory mediators including TNF-α, IL-6, and NO in joint fluid. KLF2 and iNOS expression in vitro was induced by TNF-α and KLF2 knockdown significantly reduced the TNF-α-induced iNOS expression. These findings indicate that KLF2 influences synovial inflammation in CIA mice by regulating iNOS production in synoviocytes.