title: Metallothioneins I/II expression in rat strains with genetically different susceptibility to experimental autoimmune encephalomyelitis.
abstract: OBJECTIVE
  Compared to the Dark Agouti (DA), the Albino Oxford (AO) rat strain exhibits lower susceptibility to the induction of experimental autoimmune encephalomyelitis (EAE). Here, we investigated the potential contribution of the heavy metal-binding proteins metallothioneins (MTs) I/II to these effects.
  
  
  METHODS
  Rats were immunized with bovine brain homogenate emulsified in complete Freund's adjuvant or only with complete Freund's adjuvant. The expression patterns of MTs mRNA and proteins and tissue concentrations of Zn2+ and Cu2+ were estimated in the brain and in the liver on days 7 and 12 after immunization, by real-time PCR, immunohistochemistry and inductively coupled plasma spectrometry, respectively. Additionally, the hepatic transforming growth factor beta and nuclear factor kappa B immunoreactivities were tested.
  
  
  RESULTS
  Clinical signs of EAE were not induced in AO rats, but they upregulated the expression of MT I/II proteins in the brain (hippocampus and cerebellum) and in the liver, similarly as DA rats. The transcriptional activation of MT-I occurred, however, only in DA rats, which accumulated also more zinc in the brain and in the liver. In contrast, intact AO rats had greater hepatic MT-I mRNA immunoreactivity and more Cu2+ in the hippocampus. Besides, in immunized AO rats a high upregulation of transforming growth factor beta and nuclear factor kappa B immunoreactivities was found in several hepatic structures (vascular endothelium, Kupffer cells and hepatocytes).
  
  
  CONCLUSIONS
  Our data show that AO and DA rats differ in constitutive and inductive MT-I gene expression in the brain and in the liver, as well as in the hepatic cytokine profile, suggesting that these mechanisms may contribute to the discrepancy in the susceptibility to EAE.
authors.affiliation: Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grubić-Kezele
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Jakovac
authors.forename: Marin
authors.initials: M
authors.lastname: Tota
authors.forename: Gordana
authors.initials: G
authors.lastname: Canadi-Jurešić
authors.forename: Vesna
authors.initials: V
authors.lastname: Barac-Latas
authors.forename: Cedomila
authors.initials: C
authors.lastname: Milin
authors.forename: Biserka
authors.initials: B
authors.lastname: Radošević-Stašić
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005620:Freund's Adjuvant / Q000633:toxicity; D005786:Gene Expression Regulation / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D005620:Freund's Adjuvant; D008668:Metallothionein