TLRs are very important players to regulate innate immune responses. TLR4 controls the
host defense by sensing an exotic pathogen, such as lipopolysaccharides. At the same time, some
endogenous proteins, including HMGB1 and S100A8, could also function to be a ligand to elicit
inflammatory reactions. These facts make TLR4 signaling system very complicated. For instance, the
application of TLR4 ligands in cancer therapies is desirable for enhancement of anti-tumor immunity
in terms of its reparative nature, but undesirable for enhancement of metastatic growth of cancer
cells. In this manuscript, in order to make a novel molecular design to disrupt an interaction between TLR4/MD-2 and
endogenous ligands, we provide a potential binding style of the TLR4/MD-2 complex with HMGB1 by using their 3D
structural data and docking simulations, and also discuss S100A8 binding to TLR4/MD-2.
Keywords: Endogenous ligand, HMGB1, immunity, inflammatory, S100A8, TLR4/MD-2.
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