Inhibition of the TIRAP-c-Jun interaction as a therapeutic strategy for AP1-mediated inflammatory responses


Srivastava M., Saqib U., BANERJEE S. , Wary K., Kizil B., Muthu K., ...Daha Fazla

INTERNATIONAL IMMUNOPHARMACOLOGY, cilt.71, ss.188-197, 2019 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 71
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.intimp.2019.03.031
  • Dergi Adı: INTERNATIONAL IMMUNOPHARMACOLOGY
  • Sayfa Sayıları: ss.188-197

Özet

Bacterial endotoxin-induced sepsis causes 30-40% of the deaths in the intensive care unit (ICU) globally, for which there is no pharmacotherapy. Lipopolysaccharide (LPS), a bacterial endotoxin, stimulates the Toll-like receptor (TLR)-4 signalling pathways to upregulate the expression of various inflammatory mediators. Here, we show that the TIRAP and c-Jun protein signalling complex forms in macrophages in response to LPS stimulation, which increases the AP1 transcriptional activity, thereby amplifying the expression of inflammatory mediators. Using a computer-aided molecular docking platform, we identified gefitinib as a putative inhibitor of the TIRAP-c-Jun signalling complex.