Naslov
Hepatic and thymic overexpression of endoplasmic reticulum heat shock protein gp96 induced by stress and breakdown of morphostatis

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

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

Izvornik
Abstracts of 5th International Symposium on CD1/NKT cells / Masaru Taniguchi et al. - Kamakura, 2009, ..-..

Skup
The 5th International Symposium on CD1/NKT cells

Mjesto i datum
Kamakura, Japan, 23.03.2009. - 27.03.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
heat shock proteins; gp96; liver; thymus.

Sažetak
Glucose regulated proteins, such as Grp94 (gp96), Grp78 (BiP), Grp58, calnexin and calreticulin are located primarily in the rough endoplasmic reticulum, where they interact with many secretory and membrane proteins during course of their maturation, functioning as chaperones that monitor the folding and assembly of glycoproteins. In addition, when released in forms of complexes with self peptides from damaged, infected, stressed or transformed cells, they may act as endogenous danger-associated signal that participates in stimulation of innate immune system and in generation of both-antigen specific and non-specific T cell response. Hypothesizing that gp96, as natural carrier of self-peptides may participate in the activation of self-reactive CD1-dependent NKT cells and specialized CD25+CD4+ T regulatory cells, in this report we investigated the tissue expression of gp96 in the thymus, liver and spleen: 1) after breakdown of morphostasis induced by partial hepatectomy and 2) in psychosocial stress induced by closure of mice in metabolic chamber. The data, evaluated by immunohistochemistry and real time PCR, were correlated with phenotype and cytotoxicity of hepatic and splenic mononuclear lymphatic cells (MNLC) against the NKT- and NK-cells sensitive targets. In both experimental models high overexpression of gp96 was found in the liver, as well as in the thymus (in the cortex and at cortico-medullary junction). Simultaneously, in the liver accumulated CD3intermediate/NK1.1+/CD69+cells and CD4+CD25+FoxP3+ cells, while hepatic and splenic MNLC became highly cytotoxic against syngeneic thymocytes and YAC-1 targets, implying that during the disturbance of morphostasis gp96 probably acts as a natural adjuvant for chaperoning of self peptides into the immune surveillance pathway, leading to activation of autoreactive clones NKT and Treg cells that participate in reestablishment of self tolerance.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA