Inflammation, damage repair and liver fibrosis--role of cytokines and different cell types

Abstract

Liver fibrosis is defined as an excessive deposition of extracellular matrix. It is the main complication of chronic liver damage and its endpoint, the liver cirrhosis, is responsible for impressive morbidity and mortality. The accumulation of extracellular matrix proteins in liver fibrosis and cirrhosis is due to different cell types which acquire a myofibroblastic phenotype--the hepatic stellate cells, located in the space of Disse, portal fibroblasts as well as myofibroblasts of the portal and pericentral areas. Further studies also suggest an impressive role of bone marrow-derived myofibroblasts. Differences have been reported between the two cell populations with respect to myofibroblastic differentiation, activation and "deactivation", proliferation and apoptosis. However, in most cases additional confirmation may be required; thus the biological and biochemical characterization of these cells, their interactions with inflammatory cells and the cytokine environment leading to their activation or cell death are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and regeneration. All this information is required to estimate the value of already suggested possible treatments to specifically and efficiently target the cells responsible for the development of liver fibrosis/cirrhosis and as well as for liver regeneration.