Nový buněčný model makrofágů s hepatocyty pro studium zánětlivých onemocnění jater
Kupffer cells (liver macrophages) are important immune cells in the pathogenesis of liver diseases, including nonalcoholic steatohepatitis (NASH). During these conditions, immune cells interact with and affect hepatocytes via cytokine secretion. Currently, there is no established cellular model of human immune cells with parenchymal hepatocytes to study inflammatory liver diseases. Recently, a co-culture model of THP-1 monocyte cells and hepatocarcinoma HepG2 cells has been published for studies of toxicity, insulin resistance and inflammation.
The aim of this project is to introduce in vitro model in our laboratory and validate it with respect to inflammatory pathogenesis in the liver. In addition, we would like to extend this model and use differentiated HepaRG cells or primary human hepatocytes, which possess metabolic activity and gene expression profile of normal (non-tumour) hepatocytes. THP-1 monocytes will be maturated to macrophages and subsequently co-cultured with hepatocytes. Inflammatory pathways and cytokine secretion will be studied in both macrophages and hepatocytes under different conditions. Using this model, liver inflammatory condition will be mimicked in vitro, which allow us to investigate the anti-inflammatory mechanism of Farnesoid X receptor (FXR) agonists, such as obeticholic acid, its novel derivatives or their nanoformulations targeting liver macrophages. This can help us to propose novel therapeutic interventions in diseases such as NASH.
Číslo:
GAUK1256218
Období:
01.01.2018 - 31.12.2020
Poskytovatel:
Univerzita Karlova - Grantová agentura UK
Hlavní řešitel:
Štefela Alžbeta PharmDr., Ph.D. - Farmaceutická fakulta v Hradci Králové
Celkový objem financí:
805 000,00 Kč
Interní řešitelé
Hlavní řešitel: PharmDr. Alžbeta Štefela, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Daniel Diviš
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Jana Kubačková, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Miriama Hutníková
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Bianka Šebeňová
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Mgr. Josef Škoda, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Školitel: prof. PharmDr. Petr Pávek, Ph.D.
- Univerzita Karlova,