Naslov
Glycoprotein 96 as a regulator of fetal organogenesis, embryonal implantation and compensatory liver growth

Autori
Jakovac, Hrvoje ; Mrakovčić-Šutić, Ines ; Radošević-Stašić, Biserka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
European Journal of Immunology Vol. 39 Supplement 1 / Abstracts / - , 2009, S675-S675

Skup
2nd European Congress of Immunology

Mjesto i datum
Berlin, Njemačka, 13.09.2009. - 16.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
gp96 expression; embryogenesis; liver regeneration; fetoplacental unit

Sažetak
Objectives: Imbalances in homeostasis provoked by the cellular growth at normal conditions, or by various forms of stress, initiate in the mammalian cells a highly conserved heat shock response with increased synthesis of heat shock proteins. They are involved in a variety of chaperoning functions including folding and unfolding of nascent polypeptides, protection against aggregation, specific proteolytic removal of terminally damaged polypeptides, and transport of proteins. Moreover, endoplasmic reticulum (ER)-resident HSP gp96/grp94 acts also as a natural adjuvant for priming innate and adaptive immunity, owing to its ability to stimulate APC cytokine expression and dendritic cell maturation, as well as to chaperone both MHC class I- and class II-restricted epitopes into the cross-presentation pathway of DCs. Methods: Hypothesizing that during the normal growth the discrepancies between the demand and capacities might induce ER stress that changes the gp96 expression, as well as that gp96 as natural carrier of self-peptides might participate in the breakdown of tolerance to self antigens, in this report we investigated the tissue expression of gp96 in fastly proliferating tissues during: 1) embryogenesis, 2) at fetoplacental unit during syngeneic pregnancy and 3) in regenerating liver after partial hepatectomy (pHx). In the latter model, the expression of gp96 protein and mRNA was estimated also in lymphatic organs and the changes were correlated with the appearance of self-reactive NKT and regulatory T cells and the level of cytotoxicity of lymphatic cells against the NKT and NK-sensitive targets. Results: High gp96 overexpression was found at all sites of tissue growth and remodelling (in fetal organs, in syncytiotrophoblast and chorionic vili and in regenerating liver). Moreover, pHx induced marked overexpression of gp96 in the thymus, followed by biphasic changes in the gp96 mRNA and the appearance of cytotoxic NKT and regulatory T cells (in the liver and in the thymus). Conclusion: The data point to the critical contribution of gp96 in mammalian development, embryonic-implantation and reparatory processes, implying that during the disturbance of morphostasis it serves as an endogenous danger-associated signal and a natural adjuvant, which participates in generation of autoreactive NKT and Treg cells, involved in reestablishment of self tolerance.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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