ABSTRACT
Toll-like receptor 4(TLR4)is a member of the TLRs superfamily,mainly capable of identifying bacterial endotoxin,lipopolysaccharides and lipooligosaccharides of Gram-negative bacte?ria cell walls to prevent microbial invasion. Activation of TLR4 can induce production of proinflammato?ry cytokines and inflammatory chemokines and regulate natural immunity. However,dysregulation of TLR4 can lead to autoimmune diseases. This review summarized the biological structure of TLR4 and recognition mechanisms between TLR4 and its ligands,surveyed TLR4 ligands including lipid A ana?logues,natural products and synthetic small molecules,discussed the structure-activity relationship of TLR4 modulators and the ligand-receptor and protein-protein interactions in the complex,and outlined the prospect of future research and development of TLR4 ligands.