Naslov
Upregulation of hepatic metallothioneins as early sign of developing chronic relapsing autoimmune encephalomyelitis in rats

Autori
Jakovac, Hrvoje ; Marin, Tota ; Grubić-Kezele, Tanja ; Barac-Latas, Vesna ; Mrakovčić-Šutić, Ines ; Milin, Čedomila ; Radošević-Stašić, Biserka

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

Izvornik
Ljubljana 2010, Abstracts / Schoenfeld Yehuda - Ženeva : C/o Kenes International, 2010, Abstract 896-.

Skup
7th International Congress on Autoimmunity

Mjesto i datum
Ljubljana, Slovenija, 05.05.2010. - 09.05.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
metallothionein I+II; chronic relapsing autoimmune encephalomyelitis; liver

Sažetak
Background: CR-EAE, which may be induced in genetically susceptible Dark Agouti rats, mimics many of the clinical and immunopathological features of multiple sclerosis in humans. The triggering event is invasion of peripherally activated myelin-specific immune cells in CNS, where they interact with APC and microglial cells that drive the inflammatory cascade leading to tissue damage and an amplification of the initial immune reaction. The final outcome may, however, depend on the presence of metallothioneins (MTs)-cysteine-rich heavy metal binding proteins, which have marked anti-inflammatory and neuroprotective properties. Material and methods: Since, previously, we found that attacks of CR-EAE were followed by enhanced expression of MT-I+II in both CNS and in the liver, in this study we estimated their expression before the appearance of clinical symptoms, i.e. on the 7th day after immunization of rats with bovine brain homogenate+CFA or only with CFA. Simultaneously the tissue concentrations of Zn2+ and Cu2+ were evaluated by inductively coupled plasma spectrometry. Results: Prior to any clinical manifestation of disease in the liver markedly arose the expression of MT I+II and tissue concentrations of zinc and copper. Simultaneously, in the brain increased MTs immunoreactivity, particularly on cells that form blood-brain and the blood-cerebrospinal fluid barrier and provide stimulatory signals for T cells invasion (endothelial cells, ventricular subependyma, microglia/macrophages and astroglial cells around the ventricle walls). Conclusions: The data imply that hepatic MT I+II play pivotal roles in early pathogenesis of EAE, owing to their involvement in Zn and Cu homeostasis and in mechanisms that maintain tolerance to self antigens.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA