Naslov
Effect of acute inflammation induced by lipopolysaccharide on Fas-mediated hepatocyte apoptosis in mice

Autori
Kelava, Tomislav ; Markotić, Antonio ; Ćavar, Ivan ; Turčić, Petra ; Šućur, Alan ; Ivčević ; Flegar, Darja ; Grčević, Danka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
4 th European Congress of Immunology - ECI 2015

Mjesto i datum
Beč, Austrija, 06.09.2015. - 09.09.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
apoptosis. liver injury; lipopolysaccharide; inflammation

Sažetak
Fas/Fas ligand (FasL) apoptotic pathway is involved in the pathogenesis of various liver diseases. The exact effects of inflammation on the liver apoptotic processes are still not well understood. We investigated the effect of acute inflammatory response on Fas/FasL-mediated hepatocyte apoptosis using a model of lipopolysaccharide (LPS)-induced acute inflammation. Male C57BL/6 mice received intraperitoneal injection of LPS (0.1 μg/g) while the control group of animals received the vehicle (sterile saline). After 2 hours both groups were treated with anti-Fas activating antibody (0.25 μg/g, intravenously). Mice were sacrificed after additional 6 hours and plasma (ALT, AST) and liver (pathohistology, caspase activity, qPCR) were harvested. Mice pre-treated with LPS had lower levels of ALT (median (IQR) ; 82 (32-182) vs 3709 (1429 - 5922) U/L, p=0.02) and AST 151.5 (96-256) vs 3137 (1378-5389) U/L, p=0.02) in plasma, lower number of apoptotic cells on pathohistological analysis and lower caspase 8 activity than mice in the group receiving only anti-Fas treatment. LPS alone had no effect on aminotransferase levels and caspase 8 activity, while it increased expression of inflammatory mediators TNF-alpha, IL-1 and IL-6 in hematopoietic liver cells as well as the expression of Fas and antiapoptotic CFLAR and Bcl2l1 in hepatocytes. Acute inflammation induced by LPS protects hepatocytes from Fas/FasL-mediated apoptosis by acting on Fas-apoptotic pathway upstream of caspase 8 activation. We intend to define protective mechanism more precisely by investigating effects of LPS on expression pattern of broader spectrum of pro- and anti-apoptotic molecules at various time points following LPS treatment

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA