engleski

Endoplasmic reticulum-resident heat shock protein gp96 as an innate sensor of damage induced by tissue remodelling, stress and bacterial peptidoglycan

Tissue disintegration after injury leads in the endoplasmic reticulum (ER) to activation of adaptive pathways known as the ER stress response. It is directed to correction of unfolded proteins, to the activation of proteasome-dependent ER-associated degradation of the misfolded proteins or to activation of protein translation to modulate the polypeptide traffic into the ER. Since, in these events a crucial role plays gp96, which acts not only as a molecular chaperone but also as an adjuvant, able to induce the specific immune responses against tumours and some bacteria, in this study we analysed its role in conditions of: 1) normal growth, induced by partial hepatectomy, 2) in psychosocial stress without the tissue lesions and 3) after the treatment with bacterial peptidoglycan-monomer (PGM) and PGM-Zn. Tissue expression of Gp96 protein and mRNA was estimated in liver, thymus and spleen and the data were correlated with phenotype and cytotoxicity of hepatic and splenic mononuclear lymphatic cells (MNLC) against the syngeneic thymocytes, NK and LAK-sensitive targets. All procedures induced fast cytoplasmic overexpression of gp96 staining in hepatocytes, followed by surface expression of gp96 on MNLC and upregulation of gp96 mRNA in the spleen and in the thymus. Simultaneously, in the liver accumulated CD3intermediate/NK1.1+/CD69+cells, while hepatic and splenic MNLC became highly cytotoxic against syngeneic thymocytes and YAC-1 and P815, implying that during the disturbance of morphostasis gp96 may serve as a natural adjuvant for chaperoning antigenic self peptides into the immune surveillance pathways, resulting in activation of autoreactive NKT clones with morphogenetic potential (Supported by grants from Croatian Ministry of Science).

heat stress protein gp96; liver regeneration; stress; peptidoglycan monomer

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