Background & aims In the context of liver regeneration macrophages play an important regulatory role. Thereby the changes of the composition of the different macrophage populations and of their polarization during liver regeneration has not been investigated in detail. Likewise, the factors that mainly control this process as well as their relevance for undisturbed regeneration are unclear.
Einleitung TGFβ ist an der Regulation entzündlicher Prozesse beteiligt. Da der Verlauf entzündlicher und auch regenerativer Prozesse im Körper maßgeblich durch Immunzellen reguliert wird und hierbei Makrophagen, die sich ihrem jeweiligen Mikromilieu anpassen, eine wichtige Rolle spielen, ist der Einfluss von TGFβ auf diese Zellen von besonderem Interesse.
Background & aims Macrophages are key components of the innate immune response. With high plasticity they adapt their phenotype to distinct challenges. As first responders towards pathogens they express inflammatory cytokines and chemokines that regulate responses of the cellular microenvironment within the liver. Hepatocytes represent a prime site of viral replication upon cytomegalovirus (CMV) infection. So far it is unknown, how macrophages impede viral replication in hepatocytes or if at all. Contrariwise, the impact of hepatocytes on the macrophages” phenotype in case of CMV infection remains to be elucidated. In addition, similarities or differences between co-cultivated macrophages and hepatocytes after treatment with CMV or lipopolysaccharide (LPS) are not identified, yet. First, this study aims to evaluate the pathogen-induced molecular pattern that directs the intercellular communication between macrophages and hepatocytes. Second, the impact of macrophages on viral replication within hepatocytes is analyzed.
Background & aims The liver contributes to innate immunity towards pathogens by the synthesis of acute phase proteins (APP). These proteins minimize tissue damage and promote repair processes. They isolate and neutralize invading pathogens and prevent further pathogen entry. Some of them including the antimicrobial peptide hepcidin also maintain iron homeostasis. The expression of APP by hepatocytes is regulated by inflammatory cytokines and chemokines, which are released by non-parenchymal cells like macrophages and tightly controlled by the intracellular MAPKAP kinase (MK)2. So far, it is unknown, if MK2 plays a role for the synthesis of APP in the liver. Aim of this study is to reveal MK2-dependent mechanisms involved in the regulation of APP and in particular hepcidin expression.