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KMID : 1034820090050020141
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Molecular & Cellular Toxicology
2009 Volume.5 No. 2 p.141 ~ p.146
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Cadmium but not Mercury Suppresses NF-B Activation and COX-2 Expression Induced by Toll-like Receptor 2 and 4 Agonists
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Ahn Sang-Il
Park Seul-Ki
Lee Mi-Young
Youn Hyung-Sun
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Abstract
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Toll-like receptors (TLRs) induce innate immune responses by recognizing conserved microbial structural molecules. All TLR signaling pathways culminate in the activation of nuclear factor kappa-B (NF-B) leading to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Deregulated activation of TLRs can lead to the development of severe systemic inflammation. Divalent heavy metals, cadmium and mercury, have been used for thousands of years. While cadmium and mercury are clearly toxic to most mammalian organ systems, especially the immune system, their underlying toxic mechanism(s) remain unclear. Here, we report biochemical evidence that cadmium, but not mercury, inhibits NF-B activation and COX-2 expression induced by TLR2 or TLR4 agonists, while cadmium does not inhibit NF-B activation induced by the downstream signaling component of TLRs, MyD88. Thus, the target of cadmium to inhibit NF-B activation may be upstream of MyD88 including TLRs themselves, or events leading to TLR activation by agonists.
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KEYWORD
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Cadmium, Mercury, Toll-like receptor, Cyclooxygenase-2, Nuclear factor-B
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