Wigmore S J, Fearon K C, Maingay J P, Lai P B, Ross J A
University Department of Surgery, Royal Infirmary of Edinburgh, United Kingdom.
Am J Physiol. 1997 Oct;273(4):E720-6. doi: 10.1152/ajpendo.1997.273.4.E720.
During the course of studies designed to identify the role of cytokines in the reprioritization of hepatic protein synthesis associated with cachexia we detected a hepatocyte-stimulating moiety in the supernatants of pancreatic cancer cells that was unrelated to interleukin (IL)-6. This study identifies that moiety as IL-8 and investigates the role of IL-8 in the induction of acute-phase protein production. The human pancreatic cancer cell line MIA PaCa-2 produced >1 ng/ml of IL-8 per 24 h, and supernatants from this cell line induced C-reactive protein (CRP) production from isolated human hepatocytes. Addition of neutralizing anti-human IL-8 antibody to such supernatants produced almost complete inhibition of CRP production. The addition of recombinant human IL-8 to hepatocytes resulted in a dose-dependent increase in CRP, alpha1-acid glycoprotein, and alpha1-antichymotrypsin production and a decrease in the production of transferrin and prealbumin. This study demonstrates that recombinant or tumor-derived IL-8 can modulate acute-phase protein production from isolated human hepatocytes and from human hepatoma cells.
在旨在确定细胞因子在恶病质相关的肝脏蛋白质合成重新排序中的作用的研究过程中，我们在胰腺癌细胞的上清液中检测到一种与白细胞介素（IL）-6无关的肝细胞刺激成分。本研究确定该成分是IL-8，并研究了IL-8在诱导急性期蛋白产生中的作用。人胰腺癌细胞系MIA PaCa-2每24小时产生>1 ng/ml的IL-8，该细胞系的上清液可诱导分离的人肝细胞产生C反应蛋白（CRP）。向此类上清液中加入中和性抗人IL-8抗体几乎完全抑制了CRP的产生。向肝细胞中添加重组人IL-8导致CRP、α1-酸性糖蛋白和α1-抗糜蛋白酶的产生呈剂量依赖性增加，而转铁蛋白和前白蛋白的产生减少。本研究表明，重组或肿瘤来源的IL-8可调节分离的人肝细胞和人肝癌细胞的急性期蛋白产生。
