Fluorofenidone Attenuates Inflammation by Inhibiting the NF-κB Pathway

Background Accumulated evidence indicates that inflammation plays a critical role in the progression of many renal diseases. Fluorofenidone (AKF-PD) has been shown to attenuate renal fibrosis in a number of experimental renal fibrosis models. The aim of this study was to assess the anti-inflammatory effect of AKF-PD. Methods Human proximal tubule (HK-2) cells were stimulated with tumor necrosis factor (TNF)-α in the presence or absence of AKF-PD. Mouse peritoneal macrophages were incubated with necrotic MES-13 cells in the presence or absence of AKF-PD. The production of pro-inflammatory cytokines and chemokines was measured by enzyme-linked immunosorbent assay, and the activation of Nuclear factor kB (NF-κB) pathway was assessed by Western blot analysis. Results AKF-PD significantly inhibited TNF-α-induced expression of interleukin-6, monocyte chemoattractant protein-1 and interleukin-8 and nuclear translocation of p65 in HK-2 cells. Addition of AKF-PD also significantly suppressed necrotic cell-induced TNF-α expression and p65 nuclear translocation in mouse peritoneal macrophages. Conclusions These results demonstrated that AKF-PD exerts anti-inflammatory effect, at least in part, through inhibition of the NF-κB pathway.