Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4.

Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Research Abstract Details 

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Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Abstract Text:

Hyung S Youn,Joo Y Lee,Shin I Saitoh,Kensuke Miyake,Daniel H Hwang,

Toll-like receptors (TLRs), which are activated by invading microorganisms or endogenous molecules, evoke immune and inflammatory responses. TLR activation is closely linked to the development of many chronic inflammatory diseases including rheumatoid arthritis. Auranofin, an Au(I) compound, is a well-known and long-used anti-rheumatic drug. However, the mechanism as to how auranofin relieves the symptom of rheumatoid arthritis has not been fully clarified. Our results demonstrated that auranofin suppressed TLR4-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme. This suppression was well correlated with the inhibitory effect of auranofin on the homodimerization of TLR4 induced by an agonist. Furthermore, auranofin inhibited NF-kappaB activation induced by MyD88-dependent downstream signaling components of TLR4, MyD88, IKKbeta, and p65. IRF3 activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by auranofin. Our results first demonstrate that auranofin suppresses the multiple steps in TLR4 signaling, especially the homodimerization of TLR4. The results suggest that the suppression of TLR4 activity by auranofin may be the molecular mechanism through which auranofin exerts anti-rheumatic activity.

Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Publishing Authors By Initials

HS Youn,JY Lee,SI Saitoh,K Miyake,DH Hwang,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research

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Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Biochemical and biophysical research communication

VOLUME: 350

Page Numbers: 866-71

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 0006-291X

DAY: 28

MONTH: 09

YEAR: 2006

Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372516

Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Keywords Mesh Terms:

KEYWORDS: Toll-Like Receptor 4

MESH TERMS: metabolism

Chemical & Substance for Abstract: Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Information

Substance Name: Gold

Registry Number: 7440-57-5

Grant and Affiliation Information for Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4.

AFFILIATION: USDA, ARS, Western Human Nutrition Research Center, Department of Nutrition, University of California, Davis, CA 95616, USA. hyoun@suv.ac.kr

Country: United States

AGENCY: United States NIDDK

GRANT: DK41868

ACRONYM: DK

MEDLINETA: Biochem Biophys Res Commun

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