HUMAN KUPFFER CELLS SECRETE IL-10 IN RESPONSE TO LIPOPOLYSACCHARIDE (LPS) CHALLENGE
HUMAN KUPFFER CELLS SECRETE IL-10 IN RESPONSE TO LIPOPOLYSACCHARIDE (LPS) CHALLENGE
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DOI：
10.1016/0168-8278(95)80433-1
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发表时间：
1995-02-01
影响因子：
25.7
通讯作者：
GERKEN, G
中科院分区：
文献类型：
--
作者：
KNOLLE, P;SCHLAAK, J;GERKEN, G
背景/目标：枯否细胞通过分泌细胞因子和直接的细胞接触参与肝脏中的局部免疫调节，它们能够影响其他肝细胞的功能，即窦状内皮细胞、Ito细胞和肝细胞。枯否细胞的三种已知的主要功能是从门静脉循环中清除内毒素、释放可溶性介质和呈递抗原。通过胶原酶灌注然后离心淘析分离人枯否细胞，并在培养3天后分析细胞因子分泌。我们发现，新鲜分离的人库普弗细胞分泌抗炎细胞因子白细胞介素-10以响应脂多糖的刺激，IL-10的释放在脂多糖刺激后12-24 h达到最大值。此外，我们可以表明外源性IL-10下调了脂多糖刺激后枯否细胞释放促炎细胞因子IL-6和肿瘤坏死因子α，刺激后24小时白细胞介素-6的释放达到最大，白细胞介素-10在6小时后抑制白细胞介素-6的释放。肿瘤坏死因子a在刺激后6 h表现出最大分泌，外源性白细胞介素-10也在6 h后下调肿瘤坏死因子a的释放。库普弗细胞在生理上暴露于门静脉血中存在的脂多糖，鉴于白细胞介素-10的已知抗炎作用，我们的研究结果表明，库普弗细胞对脂多糖的反应是分泌白细胞介素-10，而外源性白细胞介素-6和肿瘤坏死因子-a在体外抑制库普弗细胞的释放。10表明白细胞介素-10在肝窦局部免疫应答的调节中具有重要作用。
Background/Aims: Kupffer cells are involved in local immunoregulation in the liver by secretion of cytokines and direct cellular contact, They are able to influence the function of other liver cells, i.e. sinusoidal endothelial cells, Ito cells and hepatocytes, The three known major functions of Kupffer cells are clearance of endotoxin from the portal circulation, release of soluble mediators and presentation of antigen.Methods: Human Kupffer cells were isolated by collagenase perfusion followed by centrifugal elutriation and analyzed for cytokine secretion after 3 days in culture.Results: We found that freshly isolated human Kupffer cells secreted the anti-inflammatory cytokine interleukin-10 in response to stimulation with lipopolysaccharide, The release of interleukin-10 was maximal 12-24 h after lipopolysaccharide challenge, Furthermore, we could show that exogenous interleukin-10 downregulated the release of the proinflammatory cytokines interleukin-6 and tumor necrosis factor a by Kupffer cells after lipopolysaccharide stimulation, The release of interleukin-6 was maximal 24 h after stimulation and interleukin-10 inhibited interleukin-6 release after 6 h. Tumor necrosis factor a showed maximal secretion 6 h after stimulation and exogenous interleukin-10 also downregulated the tumor necrosis factor a release after 6 h.Conclusions: Kupffer cells are exposed physioliogically to lipopolysaccharide present in portal venous blood, Given the known anti-inflammatory effect of interleukin-10, our findings of secretion of interleukin-10 by Kupffer cells in response to lipopolysaccharide and suppression of interleukin-6 and tumor necrosis factor a release by Kupffer cells in vitro through exogenous interleukin-10 suggest an important role for interleukin-10 in the regulation of the local immune response in the liver sinusoid.