Hepatic Expression of Metallothionein I/II, Glycoprotein 96, IL-6, and TGF-βin Rat Strains with Different Susceptibilities to Experimental Autoimmune Encephalomyelitis

Abstract

In a search of peripheral factors that could be responsible for the discrepancy in susceptibility to EAE in Albino Oxford (AO) and Dark Agouti (DA) rats, we estimated the expression of metallothioneins I/II (MT), heat shock protein-gp96, interleukin (IL)-6, and transforming growth factor (TGF)-β in the livers of these animals. Rats were immunized with bovine brain homogenate (BBH) emulsified in complete Freund adjuvant (CFA) or only with CFA. Western blot and immunohistochemical analyses were done on day 12 after the immunization, as well as in intact rats. The data have shown that during the first attack of EAE only the EAE prone-DA rats markedly upregulated the hepatic MTs, gp96, IL-6, and TGF-β. In contrast, AO rats had a significantly higher expression of MT I/II, IL-6, and TGF-β in intact liver (P < 0,001), suggesting that the greater constitutive expression of these proteins contributed to the resistance of EAE. Besides, since previously we found that AO rats reacted on immunization by an early upregulation of TGF-β on several hepatic structures (vascular endothelium, Kupffer cells, and hepatocytes), the data suggest that the specific hepatic microenvironment might contribute also to the faster recovery of these rats from EAE.

Metallothionein 1: A New Spotlight on Inflammatory Diseases

“…Inflammatory cytokines such as IL-6 and TFN-a and oxidative stress found in MS lesions were most likely responsible for MT induction (80)(81)(82). These results are consistent with previous research on MT1 and MT2 expression during experimental autoimmune encephalomyelitis (EAE), a relevant preclinical animal model of MS (21,(83)(84)(85)(86)(87)(88)(89)(90). Therefore, the expression profile of MT1 and MT2 might be a useful predictor of clinical signs of MS.…”