The toll-like receptors (TLRs) are type I transmembrane proteins characterized by an extracellular domain containing leucine-rich repeats (LRRs) and a cytoplasmic tail that contains a conserved region called the Toll/IL-1 receptor (TIR) domain. These proteins have a key role in the innate immune system. They exist in the cells of lymphoid tissues and non-lymphoid tissues. Expression levels of different types of TLRs in tissues and cells vary considerably. At least 13 members of the TLR family have been identified. TLR4 is predominantly activated by lipopolysaccharide, and also it senses endogenous ligands including hyaluronic acid, oxidized low-density lipoprotein, and heat-shock proteins. Binding of TLR4 with its ligand triggers a cascade of cellular signals through the Toll/interleukin (IL)-1 receptor (TIR), leading to the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signal transduction pathways, consequently inducing expression of inflammatory genes.
