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GIST, 현 가톨릭대학교

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Biochem. Pharmacol., 2008 Jan 15;75(2):494-502 | https://doi.org/10.1016/j.bcp.2007.08.033 Cinnamaldehyde suppresses toll-like receptor 4 activation mediated through the inhibition of receptor oligomerization

Hyung S. Youn^a,1, Jun K. Lee^b,1, Yong J. Choi^b, Shin I. Saitoh^c, Kensuke Miyake^c, Daniel H. Hwang^d, Joo Y. Lee^b

^aDepartment of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam, 336-745, Republic of Korea
^bDepartment of Life Science and Research Center for Biomolecular Nanotechnology, Gwangju Institute of Science and Technology, Gwangju, 500-712, Republic of Korea
^cDivision of Infectious Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan
^dUSDA, ARS, Western Human Nutrition Research Center, and Department of Nutrition, University of California, Davis, CA 95616, USA

Corresponding author: Joo Y. Lee

Abstract

Toll-like receptors (TLRs) play a critical role in induction of innate immune and inflammatory responses by recognizing invading pathogens or non-microbial endogenous molecules. TLRs have two major downstream signaling pathways, MyD88- and TRIF-dependent pathways leading to the activation of NFkappaB and IRF3 and the expression of inflammatory mediators. Deregulation of TLR activation is known to be closely linked to the increased risk of many chronic diseases. Cinnamaldehyde (3-phenyl-2-propenal) has been reported to inhibit NFkappaB activation induced by pro-inflammatory stimuli and to exert anti-inflammatory and anti-bacterial effects. However, the underlying mechanism has not been clearly identified. Our results showed that cinnamaldehyde suppressed the activation of NFkappaB and IRF3 induced by LPS, a TLR4 agonist, leading to the decreased expression of target genes such as COX-2 and IFNbeta in macrophages (RAW264.7). Cinnamaldehyde did not inhibit the activation of NFkappaB or IRF3 induced by MyD88-dependent (MyD88, IKKbeta) or TRIF-dependent (TRIF, TBK1) downstream signaling components. However, oligomerization of TLR4 induced by LPS was suppressed by cinnamaldehyde resulting in the downregulation of NFkappaB activation. Further, cinnamaldehyde inhibited ligand-independent NFkappaB activation induced by constitutively active TLR4 or wild-type TLR4. Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.

논문정보

형식Research article
게재일2008년 01월 (BRIC 등록일 2022-12-29)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학
피인용횟수120회 이상 인용된 논문

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