Browsing by Subject "CD91"

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    Endoplasmic reticulum resident heat shock protein-gp96 as morphogenetic and immunoregulatory factor in syngeneic pregnancy
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Jakovac, Hrvoje; Grebić, Damir; Grubić-Kezele, Tanja; Mrakovčić-Šutić, Ines; Rukavina, Daniel; Radošević-Stašić, Biserka
    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 and prevent the formation of functionless aggregates of misfolded proteins, targeting them to degradation by a the ubiquitin-proteasome system. In addition, the endoplasmic reticulum (ER)-resident HSPs, such as gp96/GRP94 may, after binding to CD91 and TLRs, elicit antigen-specific and antigen-unspecific immune responses, owing to its peptide-chaperoning capacity and ability to activate APCs. Considering these properties, we examined tissue expression of gp96 at the maternal-fetal interface and in the maternal liver and spleen on the 16th day of undisturbed syngeneic pregnancy and after the treatment with peptidoglycan monomer linked with zinc (PGMZn). The data showed that in undisturbed pregnancy the gp96, CD91 and TLR2 were markedly expressed on extravillous and villous trophoblast. PGM-Zn enhanced these findings, as well as the number of uterine natural killer cells and local NFκB immunoreactivity. Gp96 expression arose also in the maternal spleen and liver, where an accumulation of NKT cells or γδT lymphocytes was seen. The data point to roles of gp96 in maintenance of proteostasis and local and systemic immune balance in pregnancy complicated by infection.
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    Thymic alterations induced by partial hepatectomy: upregulation of glycoprotein 96, CD91 and TLR2 and generation of regulatory T cells
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Jakovac, Hrvoje; Ćuk, Mira; Trobonjača, Zlatko; Mrakovčić-Šutić, Ines; Radošević-Stašić, Biserka
    Glycoprotein 96 (gp96) is an endoplasmic reticulum (ER)-resident heat shock protein. It controls the folding of nascent membrane-spanning and secretory proteins, participates in stress-induced unfolded protein response (UPR) and in pathways leading to proteolysis of damaged proteins through ER-associated degradation pathways and chaperone-mediated autophagy. In addition, gp96 controls the steroid biosynthesis and Ca2+ homeostasis and participates in insulin-IGF/signaling pathways. Besides, owing to its peptide chaperone capacity and ability to interact with antigen-presenting cells, gp96 has been implicated in priming of innate and adaptive immunity. In an attempt to visualize the intensity of ER-stress in thymus and possible participation of gp96 in generation of auto-reactive T cell clones that were detected in regenerating liver, in this study we investigated the dynamics of gp96 expression in partially hepatectomized (pHx) and sham Hx mice. Simultaneously, we detected the thymic expression of receptors responsible for endocytosis of gp96- chaperoned peptides (CD91) and intracellular activation of ER-stress pathways (TLR2), as well as the expression of TGF-β and the distribution of CD4+CD25+FoxP3+ cells. The data have shown that both pHx and sham Hx induced an accelerated apoptosis and hypoplasia in thymus. Partial Hx induced, however, a higher expression of gp96, the translocation of the CD91, TLR2 and TGF-β immunostaining from medulla to cortex and an appearance of Treg cells. The data show that pHx triggers in thymus the ERstress and UPR response and suggest that gp96 participates in the generation of natural Treg cells, which might be involved in the control of liver regeneration in the periphery.