Inflammatory pathways in liver homeostasis and liver injury

摘要

The liver is an exceptional organ in terms of its metabolic, synthetic and detoxifying function. It has the unique potential to regenerate after tissue loss and, for instance, plays an important role in the regulation of blood glucose or blood lipids. All these and many other functions represent the organ's ability to execute the proper reaction towards the body's demands and keeping it in homeostasis. The central function of the liver for homeostasis and inflammatory responses is also underscored by its sole anatomical location, allowing continuous blood supply not only from the arterial system (hepatic arteries) but also from the gastrointestinal tract via the portal vein (Figure 1). Circulating blood cells, e.g. from the innate or adaptive immune system, are pressed through a network of sinusoids allowing contact to a variety of intrahepatic cell populations such as parenchymal liver cells (hepatocytes), endothelial cells, liver-resident macrophage (Kupffer cell) or lymphocyte (mainly NKT cells) populations, hepatic stellate cells and others (Figure 1). Communication between these cell types and the regulation of hepatic functions is primarily achieved by cytokines. Cytokines are small molecular weight messengers secreted by one cell to alter the behaviour of the cell itself (autocrine messenger), a closely related cell (paracrine messenger) or cells in different organs (endocrine messenger). This chapter will highlight some of the relevant cytokines and mediators for liver homeostasis and will discuss the manifold consequences of cytokine-driven activation of hepatocellular signalling pathways in liver homeostasis and injury.