1990
DOI: 10.1016/0168-8278(90)90073-z
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Leukotriene inhibitors modulate hepatic injury induced by lipopolysaccharide-activated macrophages

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Cited by 18 publications
(11 citation statements)
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“…Like MyD88, LTB 4 has also been implicated in antimicrobial defense as well as a variety of inflammatory disease states, such as atherosclerosis, ischemia-reperfusion injury, and immune responses (12). 5-LO metabolites have been suggested to participate in in vivo and in vitro LPS responses (14), but these reports were limited by the off-target effects of the pharmacologic inhibitors used (15) and by ambiguity regarding the specific 5-LO products required for TLR responses (14,(16)(17)(18). The role of specific 5-LO metabolites and receptors in various TLR- and cytokine receptor-mediated responses is therefore poorly understood.…”
Section: Introductionmentioning
confidence: 99%
“…Like MyD88, LTB 4 has also been implicated in antimicrobial defense as well as a variety of inflammatory disease states, such as atherosclerosis, ischemia-reperfusion injury, and immune responses (12). 5-LO metabolites have been suggested to participate in in vivo and in vitro LPS responses (14), but these reports were limited by the off-target effects of the pharmacologic inhibitors used (15) and by ambiguity regarding the specific 5-LO products required for TLR responses (14,(16)(17)(18). The role of specific 5-LO metabolites and receptors in various TLR- and cytokine receptor-mediated responses is therefore poorly understood.…”
Section: Introductionmentioning
confidence: 99%
“…As hepatotoxicity was demonstrated in the C57BL/6 strain mice after receiving 50 mg GalN/animal (2.270-2.500 mg GalN/kg body weight) [ 18], the pro duction of chemotactic factor by hepatocytes was exam ined by incubating the cells with 10 mM GalN in vitro. Chemotactic activity in the culture supernatant was maxi mal after 10 h of incubation.…”
Section: Discussionmentioning
confidence: 99%
“…A pathogenetic role of neutrophils and monocytes in tissue injury has been recently demonstrated in several clinical disorders [27], Histological investigation showed a prominent inflammatory infiltrate in the GalN-injured liver, and the infiltrate consisted largely of neutrophils and recently mobilized monocytes [2], Although mice are relatively resistant to GalN as compared to rabbits or rats [28], hepatotoxicity was demonstrated in the GalNtreated mice when they received LPS-activated spleen cells, especially macrophages [8], Since splenectomy has been found to reduce a grade of GalN-induced hepatic injury, spleen cells could play an important role in the pathogenesis of GalN-induced hepatitis [8], Furthermore, previous study revealed that some lipoxygenase inhibitors reduced generation of oxidative free radicals by macro phages, thus protecting against liver injury induced by GalN [ 18], In this paper, we examined the mechanism of monocyte accumulation in the GalN-injured liver and clarified the effect of lipoxygenase inhibitors on chemo taxis of spleen cells.…”
Section: Discussionmentioning
confidence: 99%
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“…Normally, intrahepatically formed LTs moderate the complex intra-organ cell-cell communication between non-parenchymal and parenchymal cells. LTs may contribute to the local regulation of carbohydrate metabolism during liver inflammation [15], may be involved in islet cell death, or hepatotoxicity or hepatobiliary dysfunction induced by STZ [16][17][18], may be causally related to the development of inflammation in estradiol-induced intrahepatic cholestasis [1], and may mediate macrophage action in LPS/GalN-induced liver injury [19]. However, no study has yet demonstrated whether chemically-induced liver injury specifically alters the metabolism or elimination of LTs.…”
Section: Introductionmentioning
confidence: 99%