Naslov
Endoplasmic reticulum resident heat shock protein Gp96 as morphogenetic and immunoregulatory factor in syngeneic pregnancy

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

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

Izvornik
NeuroImmunoModulation Vol.18/6 2011. NeuroImmunoModulation in Health and Disease: An Integrative Biomedical Approach / Del Rey Adriana and Kolbe, Ina - Basel : Karger Publishers, 2011, 400-400

Skup
8th Congress of the international Society for NeuroimmunoModulation (ISNIM) with the German Endocrine-Brain-Immune Network (GEBIN)

Mjesto i datum
Dresden, Njemačka, 22.10.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
gp96; pregnancy; fetoplacental-unit; PGM; CD91; TLR2

Sažetak
The severe remodeling of endometrial stroma during blastocyst adhesion and trophoblast invasion initiates at maternal-fetal interface the reaction of evolutionary old heat shock response, in which heat shock proteins, as molecular chaperons, monitor the configurations of newly synthesized proteins, prevent the formation of functionless aggregates or target the misfolded proteins of the endoplasmic reticulum (ER) to degradation by a the ubiquitin-proteasome system. In addition, ER-resident HSP gp96 owing to its peptide-chaperoning capacity elicits also innate and adaptive immune responses, after binding to CD91 and TLR, i.e. the receptors that mediate the endocytosis of gp96 or unspecifically activate APCs, inducing their maturation and secretion of pro-inflammatory cytokines. Considering these properties, we examined tissue expression of gp96 protein, CD91 and TLR2 at the maternal-fetal interface on the 16th day of syngeneic pregnancy and after the treatment of mice with PGM-Zn, originally isolated from a Gram (+) bacteria. At the systemic level gp96 expression was evaluated in the liver, spleen and thymus and the data were correlated with phenotype and cytotoxicity of hepatic and splenic lymphatic cells against the NKT and NK-sensitive targets. The data showed that gp96 immunoreactivity in non-gravide uterus was present only on glandular epithelium. Pregnancy, however, markedly upregulated the expression of gp96, CD91 and TLR2 on extravillous and villous trophoblast, and treatment with PGM-Zn additionally enhanced these findings. Gp96 expression arose also in the liver, spleen and thymus. Simultaneously, an accumulation of CD3intermediate/NK1.1+/CD69+cells in the liver and augmentation of NKT and NK-mediated cytotoxicity in the liver and in the spleen was seen. The data imply that gp96 and its receptors CD91 and TLR2 participate in tissue remodeling during decidualization, as well as in activation of innate and adaptive immune after disturbance of morphostasis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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