Naslov
Effect of acute inflammation induced by lipopolysaccharide on Fas-mediated hepatocyte apoptosis in mice
(Učinak akutne upale izazvane primjenom lipopolisaharida na apoptotičko oštećenje jetara pposredovano aktivacijom Fas-a u miševa)

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

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

Izvornik
Book of abstract, Croatian immunological society, 2014 annual meeting / Polić, Bojan - Rijeka, 2014, 59-60

Skup
Croatian immunological society, 2014 annual meeting

Mjesto i datum
Krk, Hrvatska, 17.09.2014. - 18.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
lipopolysaccharide; Fas; liver apoptosis
(lipopolisaharid; Fas; apoptoza jetara)

Sažetak
BACKGROUND: Fas/Fas ligand (FasL) apoptotic pathway in hepatocytes is thought to be involved in the pathogenesis of liver disease such as viral hepatitis and nonalcoholic steatohepatitis. Although it is known that various immune mediators modulate hepatocyte susceptibility to Fas/FasL- mediated apoptosis, the exact effects of pro- inflammatory cytokines on the apoptotic processes in hepatocyte are still not well understood. In our study we aimed to investigate the effect of acute inflammatory response on Fas/FasL-mediated hepatocyte apoptosis using a model of lipopolysaccharide (LPS)-induced acute inflammation. METHODS: Acute inflammation was induced in male C57BL/6 mice by intraperitoneal injection of LPS (0.1 µg/g body weight in 10 µL/g body weight of sterile saline) while the control group of animals received the same volume of sterile saline. After 2.5 hours both groups were treated with anti-Fas activating antibody (0.1 μg/g body weight, intravenously) in order to induce hepatocyte apoptosis. Mice were sacrificed after additional 6 hours and plasma (ALT, AST) and liver tissue (pathohistology, caspase activity assays, qPCR) were collected for the analyses. RESULTS: Mice pre-treted with LPS had lower levels of ALT (32 ± 11 vs 164 ± 61 U/L, p<0.01) and AST (264 ± 166 vs 952 ± 473 U/L, p=0.02) in plasma as well as lower number of apoptotic cells on pathohistological analysis than mice in the group receiving only anti-Fas treatment. Expression of inflammatory mediators TNF-alpha and IL-1 was increased in both groups compared to intact animals, without significant difference between group receiving LPS followed by anti-Fas antibodies and group receiving only anti-Fas antibodies. Also, we found no significant difference in caspase 8 activity between the groups (1 ± 0.07 (LPS + anti-Fas group) vs 1.05 ± 0.16 relative units (anti-Fas group), p= 0, 51) and qPCR analysis showed no significant difference in expression pattern of anti-apoptotic genes (Bcl-2, XIAP, CFLAR). CONCLUSION: Acute inflammation induced by LPS protects hepatocytes from Fas/FasL-mediated apoptosis by acting on Fas- apoptotic pathway downstream 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 as well as inflammatory mediators at various time points following anti-Fas treatment.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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