APP alone cannot arouse the stimulation in RAW 264.7 macrophages without LPS induction, so TLR4 seems not to be the direct ligand of APP in the macrophage. Furthermore, the synergistic activity of APP, that affects NO/TNF-a production by LPS-induced macrophages, implies that APP can enhance the expression of downstream mediators that are generated by LPS activation and the TLR4 pathway.