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Peptidoglycan monomer as a modulator of gp96 expression during liver regeneration in mice

In an attempt to analyze the possibility that damage-associated and pathogen-associated signals change the tissue expression of heat shock protein-gp96, which as molecular chaperone participates in correction of unfolded or misfolded proteins and acts as a natural adjuvant for chaperoning antigenic self peptides into the immune surveillance pathways, in this study, we analyzed its expression in: 1) partially hepatectomized mice (pHx), 2) in mice treated in vivo with peptidoglycan-monomer linked with zinc (PGM-Zn), and 3) in pHx mice treated with PGM-Zn. Gp96 proteins were determined by immunohistochemistry and the data were correlated with phenotype and cytotoxicity of hepatic and splenic mononuclear lymphatic cells (MNLC) against the NK sensitive (YAC-1) and NKT sensitive (syngeneic thymocytes) targets. It was found that each procedure markedly upregulated the gp96 expression in the liver and in the spleen, and that treatment of pHx mice with PGM-Zn additionally enhanced this expression. The later procedure increased also the proportion of NKT cells in the liver and the cytotoxicity of hepatic MNLC against YAC. In the spleen, however, PGM-Zn in combination with pHx increased only the early cytotoxicity against syngeneic thymocytes (24h after pHx), and decreased the cytotoxicity against YAC-target (24h and 48h after pHx). The data point to morphogenetic functions of gp96 during liver regeneration and suggest that PGM-Zn through Toll-like receptors or by Zn++ might affect the chaperone-mediated signaling.

peptidoglycan monomer -Zn; partial hepatectomy; liver; thymus; spleen

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