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

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.