The anti‐TLR4 monoclonal antibody Sa15‐21 enhances inflammatory cytokine production in LPS‐stimulated macrophages

Abstract

Sa15‐21, a monoclonal antibody against mouse Toll‐like receptor (TLR) 4, can protect mice from lipopolysaccharide (LPS)/D‐galactosamine‐induced acute lethal hepatitis. Herein, we investigated the molecular mechanisms underlying Sa15‐21‐mediated regulation of TLR4 signaling in macrophages. Results showed that Sa15‐21 enhanced the production of proinflammatory cytokines and attenuated the production of anti‐inflammatory cytokines in LPS‐stimulated macrophages. Western blotting analysis revealed that Sa15‐21 pretreatment had no effect on NF‐κB and MAPK signaling in LPS‐stimulated macrophages; however, Sa15‐21 treatment alone led to a weak and delayed activation of NF‐κB and MAPK signaling without any effect on proinflammatory cytokine production. By contrast, Sa15‐21 failed to induce the activation of interferon regulatory factor 3. Taken together, our results indicate that Sa15‐21 sensitizes macrophages to facilitate the inflammatory response via TLR signaling.