Effect Of Kupffer Cells Research Articles

Kupffer细胞在原发性肝癌发病机制中的作用

Kupffer细胞在原发性肝癌发病机制中的作用

Anti-inflammatory effects of Kupffer cells through α7-nicotinic acetylcholine receptors

Nicotine exerts anti-inflammatory effects in several cell types. α7-nicotinic acetylcholine receptor (α7-nAChR), which has high permeability to calcium, is believed to contribute significantly to nicotinic anti-inflammatory effects. However, the molecular mechanism is largely unknown. Kupffer cells in the liver play an important role in inflammatory response to pathogens invading, but whether there is α7-nAChR expression in Kupffer cells or cholinergic anti-inflammatory pathway involved in this process remains unclear.

Kupffer Cells Promote Hepatic Steatosis Via Interleukin-1β–Dependent Suppression of Peroxisome Proliferator-Activated Receptor α Activity

Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity.

Hepatocyte and Kupffer Cells Co-cultured on Micropatterned Surfaces to Optimize Hepatocyte Function

One strategy for temporarily extending the lives of patients with liver failure is the use of bioartificial liver (BAL) support devices. The functional components of BALs are the parenchymal liver cells known as hepatocytes. One design option for further improving current BAL performance levels is to include the non-parenchymal cells of the liver (e.g., Kupffer cells) in the design. In the current study, the effect of Kupffer cells on hepatocyte function was investigated using micropatterned co-cultures of these two liver cell populations. With traditional co-culture methods, the user is unable to control the relative proximity of one cell type to another. In this study, two different micropatterning techniques were used to engineer macro and fine micropatterned configurations for evaluating hepatocyte-Kupffer cell co-cultures. The ratio of one cell population to the other was also adjusted to evaluate the effects on hepatocyte function. The micropatterned co-cultures were maintained for ten days to evaluate for morphological and functional (e.g., albumin, urea) changes. The results illustrate that micropatterning hepatocytes, in the arrangements of this study, significantly improved hepatocyte function.

Immunomodulatory effects of kupffer cells on antigen stimulated T-lymphocyte proliferation in vitro

Immunomodulatory effects of kupffer cells on antigen stimulated T-lymphocyte proliferation in vitro

Effect of Kupffer cells on HDL 3-cholesterol reverse transport in vitro

Effect of Kupffer cells on HDL 3-cholesterol reverse transport in vitro

Kupffer cells modulate natural killer cell activity in vitro by producing prostaglandins

The effect of Kupffer cells on natural killer (NK) cell-mediated cytotoxicity was examined. Kupffer cells prepared from rat liver suppressed NK activity against K562 cells and other tumor cell lines through a soluble factor secreted into the culture supernatant. When human peripheral blood mononuclear cells were incubated with the Kupffer cell-culture supernatant, a significant reduction of the cytotoxic activity was observed in the 6-hr chromium-release assay. This activity was dose dependent and was evident at various effector/target cell ratios. Lipopolysaccharide stimulated generation of the suppressive factor released from Kupffer cells in a dose-dependent manner. Suppression of the NK activity was observed when the Kupffer cell-culture supernatant was present in the assay system, whereas pretreatment of effector/target cells with the supernatant had minimal inhibitory effects. Autologous monocytes in human peripheral mononuclear cells were not related to this suppression. The suppressive factor in the fraction had a molecular weight below 10,000. Indomethacin, an inhibitor of prostaglandin synthesis, ameliorated the suppressive effects. These results suggest that Kupffer cells may modulate NK activity by producing PGs (E 1, E 2, and F 2α).