Toll-like receptor signaling in sepsis.
Despite extensive research, bacterial sepsis and its associated systemic inflammation remain a major cause of morbidity and mortality in the pediatric intensive care unit. Advances in molecular biology, however, have improved our understanding of this disease process and have opened up new avenues of potential therapeutic approaches. One such exciting area has been the substantial and still growing evidence that the mammalian immune system uses a family of Toll-like receptors (TLRs) to generate a response to molecular patterns present on invading microorganisms. In particular, TLR4 is part of a recognition complex for bacterial lipopolysaccharide (LPS), thus raising the likelihood of its involvement in the inflammatory response to bacterial sepsis. This review highlights our understanding of the molecular biology of these receptors, focusing on the LPS response, and concluding with a summary of ongoing evaluation and potential therapeutic strategies for treating sepsis through blockade of TLR signaling.
Lakhani
Saquib A
SA
Section of Pediatric Critical Care, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Bogue
Clifford W
CW
D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018805:Sepsis / Q000139:chemically induced / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors