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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Conference Article|
September 24 2010
Exploring the LPS/TLR4 signal pathway with small molecules
Francesco Peri
;
Francesco Peri
1
1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy1
To whom correspondence should be addressed (email francesco.peri@unimib.it).
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Matteo Piazza
;
Matteo Piazza
1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy
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Valentina Calabrese
;
Valentina Calabrese
1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy
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Gaetana Damore
;
Gaetana Damore
1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy
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Roberto Cighetti
Roberto Cighetti
1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy
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Biochem Soc Trans (2010) 38 (5): 1390-1395.
Article history
Received:
April 29 2010
Citation
Francesco Peri, Matteo Piazza, Valentina Calabrese, Gaetana Damore, Roberto Cighetti; Exploring the LPS/TLR4 signal pathway with small molecules. Biochem Soc Trans 1 October 2010; 38 (5): 1390–1395. doi: https://doi.org/10.1042/BST0381390
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