earticle

영어

Tunicamyin (TM) blocks the synthesis of all N-linked glycoproteins and causes ER stress. It has been reported that TM inhibits LPS-induced NF-kB activation via suppression of MD-2 N-glycosylations. In this study, we investigated that the inhibitory effect of tunicamycin (TM) on lipopolysaccharide (LPS)-induced inflammation is independent of N-linked glycosylations of MD-2 in RAW264.7 macrophage. TM significantly suppressed nitiric oxide (NO) production, inducible nitric oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines, interleukin 1 beta (IL-1β) and tumor necrosis factor alpa (TNF-α) expression in response to LPS. TM also inhibited the inflammatory reactions in response to other TLR ligands, Polyinosinic:polycytidylic acid (Poly:IC) or Lipoteichoic acid (LTA), which do not require N-glycosylated MD-2 protein for macrophage activation. This indicates that the anti-inflammatory effect of TM may not associated with MD-2 N-linked glycosylations. Other well-known ER stress inducers, A23187 (A23) and thapsigargin (TG) had no effect on LPS-induced inflammation, suggesting that ER stress induction and UPR pathway is not necessarily stimulatory factors for LPS-induced inflammation. We showed that TM inhibited LPS-induced nuclear translocation of p50 and DNA binding of p50 and p65 to NF-κB binding sequence of iNOS promoter. Therefore we conclude that TM repressed LPS-induced inflammation through suppression of NF-kB binding activity and independent of inhibition of N-linked glycosylations of MD-2.