期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 38, 期 -, 页码 1390-1395出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST0381390
关键词
CD14; inflammation; lipic A; l-popolysaccharide (LPS); myeloid differentiation protein 2 (MD-2); Toll-like receptor 4 (TLR4)
资金
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [1R01A1059372]
The identification of the bacterial endotoxin receptors for innate immunity, most notably TLR4 (Toll-like receptor 4), has sparked great interest in therapeutic manipulation of the innate immune system. In the present mini-review, several natural and synthetic molecules that modulate the TLR4-mediated LPS (lipopolysaccharide) signalling in animals and humans are considered, and their mechanisms of action are discussed. The process of LPS sensing and signal amplification in humans is based on the sequential action of specific receptors situated in the extracellular side of the innate immunity cells, which bind and transfer LPS to TLR4: LBP (LPS-binding protein), CD14, MD-2 (myeloid differentiation protein 2). We classified the compounds active on TLR4 pathway depending on the specific molecular targets (LPS, LBP, CD14, MD-2 or TLR4). Small molecules developed by our group are described that inhibit LPS-stimulated TLR4 activation by selectively targeting the LPS-CD14 interaction. These compounds have an interesting antiseptic shock, anti-inflammatory and anti-neuropathic pain activity in vivo.
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