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.
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.
Authors: Marcus Schuchmann; Felix Ruckert; Jose F Garcia-Lazaro; Andrea Karg; Jurgen Burg; Natalia Knorr; Jurgen Siebler; Eugene E Varfolomeev; David Wallach; Wolfgang Schreiber; Ansgar W Lohse; Peter R Galle Journal: World J Gastroenterol Date: 2005-12-14 Impact factor: 5.742
Authors: Alice Y W Chang; Julie Y H Chan; Jimmy L J Chou; Faith C H Li; Kuang-Yu Dai; Samuel H H Chan Journal: J Physiol Date: 2006-05-04 Impact factor: 5.182
Authors: Jean-Philippe Pradere; Juliane S Troeger; Dianne H Dapito; Ali A Mencin; Robert F Schwabe Journal: Semin Liver Dis Date: 2010-07-21 Impact factor: 6.115
Authors: Ursula Hofer; Erika Schlaepfer; Stefan Baenziger; Marc Nischang; Stephan Regenass; Reto Schwendener; Werner Kempf; David Nadal; Roberto F Speck Journal: PLoS Pathog Date: 2010-04-29 Impact factor: 6.823