Inhibitory effect of iguratimod on TNFα production and NF-κB activity in LPS-stimulated rat alveolar macrophage cell line

AimTo investigate the effect of iguratimod (T-614), a non-steroidal anti-inflammatory drug, on TNFα mRNA expression and TNFα production, and on the activity of nuclear factor-κB (NF-κB) in the rat alveolar macrophage cell line (NR8383) activated by LPS. MethodsNR8383 cells were pretreated with T-614 (13.4, 26.7, 53.4 μmol·L^-1), then were stimulated with LPS. The production of TNFα in the supernatant of NR8383 was assayed by enzyme-linked immunosorbent assay (ELISA). The TNFα mRNA level was determined by a semi-quantitative PCR assay. Assessment of the NF-κB DNA binding activity was performed by an ELISA kit. ResultsT-614 inhibited LPS-stimulated mRNA expression and production of TNFα in a concentration-dependent manner, as well as the activity of NF-κB. The IC₅₀ value of effect of T-614 on TNFα level was 26.2 μmol·L^-1. ConclusionThe inhibitory effect of T-614 on the production of TNFα in LPS-stimulated NR8383 cells may be mediated by suppression of NF-κB activity.