Protective effect of a novel antibody against TLR2 on zymosan-induced acute peritonitis in NF-κB transgenic mice

摘要

In addition to antibiotic therapy for treatment of peritonitis, biologics have also been found to exhibit both anti-inflammatory and inflammation-resolving properties. Here, we first developed NF-κB transgenic mice with zymosan-induced acute peritonitis to investigate the effects of a novel anti-Toll-like receptor (TLR)2 antibody (anti-T20). In this mouse model, anti-T20 treatment significantly attenuated the increase of peritoneal NF-κB activity and serum levels of inflammatory cytokines, including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a dose-dependent manner compared to mice treated with isotype control antibody. Additionally, anti-T20 treatment significantly reduced MCP-1 levels as well as the leukocyte and total protein concentrations in the peritoneal exudates of peritonitis mice. Moreover, anti-T20 treatment significantly reduced TLR2 signal transduction in the leukocytes in peritoneal exudates from the experimental peritonitis mice. In conclusion, we developed a zymosan-induced acute peritonitis mouse model that facilitated visualization of NF-κB activity and demonstrated that anti-T20 treatment plays a protective role in this model concomitant with the inhibition of the zymosan-induced inflammatory response.