Galblladder expression of metallothionein I/II and zinc ions in cholecystolithiasis

Metallothioneins (MTs) are phylogenetically old cysteine-rich proteins, which may be found in all eukaryotes and some prokaryotes. Owing to high affinity for physiological metals, such as zinc and copper, they are critical components of zinc-finger transcription factors and other regulatory proteins involved in cell growth and multiplication. Besides, providing cytoprotective action against toxic heavy metals and oxidative damages of DNA, proteins, and lipid membrane structures, they participate in anti-apoptotic and anti-inflammatory pathways, as well as in immune regulation and carcinogenesis. The aim of the study was to investigate the expression of MTs in cholecystitis induced by gallstones and to correlate it with intensity of inflammation and liberation of zinc ions. Patients and methods: Gallbladder tissue samples were obtained from 25 patients subjected to laparoscopic cholecystectomy owing to the symptomatic cholecystolithiasis. According to the standard pathohistological findings and NF-B expression the tissue changes were classified as subacute and chronic cholecystitis and the expression of MT-I/II isoforms and free zinc content were visualized by monoclonal anti-MT I+II antibodies and zinc fluorophore-Zinquin. Differences between groups were assessed by Mann-Whitney U test after cell-based staining quantification of MT and Zn expressions by Cell F v3.1 software. Results: The data have shown that chronic cholecystolithiasis is followed by overexpression MTs and accumulation of labile zinc ions in gallbladder tissue (epithelium, vascular endothelium, stromal cells). Besides, in area of inflammation were found several CD3+ cells in contact with MT+ epithelial, endothelial and monocyte-like cells, as well as the CD3+/MT+ cells. Conclusion: The data point to regulatory roles of MT/zinc network in chronic pro-inflammatory environment in gallbladder tissue induced by gallstones.