|Youn, Hyung - USDA, ARS, WHNRC, UCDAVIS|
|Saitoh, Shin - UNIV. TOKYO, MED. SCI.|
|Miyake, Kensuke - UNIV. TOKYO, MED. SCI.|
Submitted to: Biochemical Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 28, 2006
Publication Date: June 28, 2006
Citation: Youn, H.S., Saitoh, S.I., Miyake, K., Hwang, D.H. 2006. INHIBITION OF HOMODIMERIZATION OF TOLL-LIKE RECEPTOR 4 BY CURCUMIN. Biochemical Pharmacology. 72(2006):62-69. Interpretive Summary: Plant polyphenols with a structural motif that confer Michael-type addition can inhibit Toll-like receptor-mediated inflammatory responses. These results provide a mechanistic base for why certain phytochemicals possess anti-inflammatory effects. These results can facilitate identifying potential anti-inflammatory agents from variety of phytochemicals.
Technical Abstract: Toll-like receptors play a key role in sensing microbial components and inducing innate immune responses. Ligand-induced dimerization of Toll-like receptor (TLR) 4 is required for the activation of downstream signaling pathways. Thus, the receptor dimerization may be one of the first lines of regulation in activating TLR-mediated signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) with a structural motif that can confer Michael-type addition, inhibit both ligand-induced and ligand-independent dimerization of TLR4. These results imply that the activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain dietary phytochemicals we consume daily.