6533b820fe1ef96bd1279a19

RESEARCH PRODUCT

HSP60 and CpG-DNA-oligonucleotides differentially regulate LPS-tolerance of hepatic Kupffer cells

Peter R. GalleMarcus SchuchmannFrank HermannRuurd Van Der ZeeAnsgar W. LohseJohannes Herkel

subject

LipopolysaccharidesMaleLipopolysaccharideKupffer CellsImmunologyGene ExpressionGalactosamineReceptors Cell SurfaceCell LineMicrobiologyMicechemistry.chemical_compoundImmune systemImmunityHeat shock proteinAnimalsImmunology and AllergyInterleukin 6Cells CulturedbiologyInterleukin-6Reverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alphaAlanine TransaminaseChaperonin 60Macrophage ActivationToll-Like Receptor 9DNA-Binding ProteinsToll-Like Receptor 4LiverOligodeoxyribonucleotideschemistryToll-Like Receptor 9Immunologybiology.proteinFemaleHSP60Tumor necrosis factor alphaLiver Failure

description

Background/aims: Hepatic Kupffer cells (KC) are major regulators of the immune response to gut-derived bacterial products; uncontrolled activation of KC by bacterial components is of pathogenic relevance in alcoholic hepatitis and septic shock. Methods: We examined the role of bacterial lipopolysaccharide (LPS), bacterial and autologous HSP60 and bacterial DNA, which are recognized by innate Toll-like receptors, during activation of murine KC. Results: In cultivated KC, autologous HSP60 induced a state of LPS-hyporesponsiveness; bacterial DNA did not mitigate the response to subsequent LPS-challenge in vitro; in contrast, pre-treatment of mice with bacterial DNA even significantly increased serum TNF levels, liver function tests and mortality in a model of LPS-induced hemorrhagic liver failure. Conclusion: HSP60 and CpG-DNA differentially modulated the threshold of KC activation by LPS and might therefore contribute to the regulation of inflammatory immunity to gut-derived bacterial compounds.

yearjournalcountryeditionlanguage
2004-05-01Immunology Letters
https://doi.org/10.1016/j.imlet.2004.03.016