Matches in SemOpenAlex for { <https://semopenalex.org/work/W1900975454> ?p ?o ?g. }
- W1900975454 endingPage "542" @default.
- W1900975454 startingPage "533" @default.
- W1900975454 abstract "In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative sepsis is associated with elevated levels of IL-1R-associated kinase M, an intracellular negative regulator of MyD88-dependent TLR signaling. In the present study, we investigated whether in vivo exposure of humans to LPS induces tolerance in circulating leukocytes to other TLR agonists that rely either on MyD88- dependent or on MyD88-independent signaling. Analysis of TNF, IL-1beta, IL-6, and IL-10 levels in whole blood demonstrated that leukocytes were hyporesponsive to ex vivo LPS restimulation 3-8 h after i.v. LPS injection (4 ng/kg). Reduced cytokine release during the same interval was also observed in whole blood further stimulated with MyD88-dependent ligands for TLR2, TLR5, and TLR7 or with whole bacteria. Strikingly, blood leukocytes were also tolerant to a ligand for TLR3, which signals solely through a MyD88-independent (Toll IL-1R domain-containing adaptor-inducing IFN-beta (TRIF)-dependent) pathway. The hyporesponsiveness of leukocytes to TLR3 ligation was associated with reduced rather than increased levels of the recently identified TRIF inhibitor SARM. Taken together, these data indicate that systemic LPS challenge of human volunteers induces cross-tolerance to multiple TLR ligands that signal in a MyD88-dependent or MyD88-independent manner and suggest that LPS exposure of human blood leukocytes may hamper the inflammatory response to various microbial components." @default.
- W1900975454 created "2016-06-24" @default.
- W1900975454 creator A5003483803 @default.
- W1900975454 creator A5041160778 @default.
- W1900975454 creator A5048965254 @default.
- W1900975454 creator A5056147201 @default.
- W1900975454 creator A5060943192 @default.
- W1900975454 creator A5069416813 @default.
- W1900975454 date "2009-07-01" @default.
- W1900975454 modified "2023-10-18" @default.
- W1900975454 title "In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands" @default.
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