alexa Therapeutic targeting of innate immunity with Toll-like receptor 4 (TLR4) antagonists.


Journal of Clinical Toxicology

Author(s): Peri F, Piazza M

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Abstract Early recognition of invading bacteria by the innate immune system has a crucial function in antibacterial defense by triggering inflammatory responses that prevent the spread of infection and suppress bacterial growth. Toll-like receptor 4 (TLR4), the innate immunity receptor of bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. TLR4 activation by bacterial lipopolysaccharide (LPS) is achieved by the coordinate and sequential action of three other proteins, LBP, CD14 and MD-2 receptors, that bind lipopolysaccharide (LPS) and present it to TLR4 by forming the activated (TLR4-MD-2-LPS)(2) complex. Small molecules active in modulating the TLR4 activation process have great pharmacological interest as vaccine adjuvants, immunotherapeutics or antisepsis and anti-inflammatory agents. In this review we present natural and synthetic molecules active in inhibiting TLR4-mediated LPS signalling in humans and their therapeutic potential. New pharmacological applications of TLR4 antagonists will be also presented related to the recently discovered role of TLR4 in the insurgence and progression of neuropathic pain and sterile inflammations. Copyright © 2011 Elsevier Inc. All rights reserved. This article was published in Biotechnol Adv and referenced in Journal of Clinical Toxicology

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