Naslov
Upregulation of heat shock protein gp96 in the liver, spleen and thymus induced by stress in mice

Autori
Grebić, Damir ; Mrakovčić-Šutić, Ines ; Jakovac, Hrvoje ; Tota, Marin ; Milin, Čedomila ; Tomac, Jelena ; Rukavina, Daniel ; Radošević-Stašić, Biserka

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

Izvornik
Final Program & Abstract Book / Crousos GP - Atena, 2005

Skup
The 6th Meeting of the International Society for NeuroimmunoModulation

Mjesto i datum
Atena, Grčka, 25.09.2005. - 28.09.2005

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
stress; heat shoch protein gp96; autoreactivity

Sažetak
Introduction: Stress proteins such as heat shock proteins (HSPs), the glucose-regulated proteins (GRPs ; gp96) and ubiquitin serve as chaperones, participating in protein synthesis and transport through the various cellular compartments. Moreover, as carriers of antigenic moieties such as peptides, these stress proteins have the ability to modulate the cellular immune response and activate the professional antigen-presenting cells (APC), resulting in the production of pro-inflammatory cytokines and up-regulation of costimulatory molecules. In an attempt to elucidate some aspects of these events in this study we investigated the effects of psychosocial stress in mice, investigating the participation of hepatic lymphoid system, metallotioneins and heat shock protein gp96, which normally reside in the endoplasmic reticulum of healthy cells. Material & Method: Experiments were done on C57/BL6 mice, which were as a group of 6 animals for 1 h/day closed in a small metabolic chamber, containing soda lime for absorption of CO2 and ventilated with fresh air. Protocol was repeated for 10 days and then gp96, metallothioneins I+II (MT) and phenotype of lymphoid cells were detected in the liver, thymus and spleen by immunohistological staining and FACScan analysis. Simultaneously the cytotoxicity of intrahepatic and splenic mononuclear lymphatic cells was tested against syngeneic thymocytes and NK-sensitive targets (YAC-1). The findings were compared with data obtained in unstressed mice, living in the normal laboratory conditions. Results: The data revealed that stress moderately upregulates the MT expression only in the hepatocytes. Expression of gp96 was, however, markedly expressed in hepatocytes, as well as in the spleen and thymus, where extensive surface staining was found on cells in the cortical and corticomedullar zones. Simultaneously, in the liver accumulated NKT cells (CD3inermediated/NK1.1+ cells) and NK cells (CD3-/NK1.1+) and hepatic MNLC became more cytotoxic against the syngeneic thymocytes (p<0.01), and less cytotoxic against the YAC-1 target. Conclusions: The data suggest that during stress conditions neuro-endocrine factors and cytokines upregulate traffics of gp96-associated peptide in the liver, activating NKT and other cells that might mediate the cytotoxicity against altered self. (Supported by grants from Croatian Ministry of Science, project No 0062018).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA