Disease relevance of Hspd1

• We found that human HSP60 (but not the Escherichia coli GroEL or the Mycobacterial HSP65 molecules) induced naive mouse B cells to proliferate and to secrete IL-10 and IL-6 [1].
• The immunopathologic sequelae of chlamydial infection are correlated with immune responses to the Chlamydia trachomatis heat shock protein 60 (hsp60) [2].
• A mycobacterial HSP65 DNA vaccine was previously shown to have prophylactic and immunotherapeutic effects against Mycobacterium tuberculosis infection in mice [3].
• In this study, the modulatory effect of interleukin (IL)-2, IL-4, and interferon (IFN)-gamma coexpressed with the 60-kDa heat shock protein (Hsp60) of Yersinia enterocolitica O:8 (Y-Hsp60) was studied [4].
• These findings indicate that encapsulated MHSP/TDM is more immunogenic than naked hsp65 DNA, and has great potential to improve vaccine effectiveness against leishmaniasis and tuberculosis [3].

Psychiatry related information on Hspd1

• Considering the abundant nature of bacterial Hsp 60 and the upregulation of this protein after Salmonella infection of eukaryotic cells, this mode of antigen presentation may be particularly relevant to understanding the host defense mechanisms against gram-negative bacteria [5].

High impact information on Hspd1

• Immunity to hsp65 can cause autoimmune diabetes in mice and may be related to autoimmune arthritis in rats and humans, so immunity to hsp65 should be forbidden; yet healthy persons manifest T-cell responses to self-hsp65 [6].
• Microbial and mammalian hsp65 molecules are 50% identical in amino acid sequence and immunologically cross-reactive, so microbial hsp65 looks like self; yet hsp65 is a dominant antigen in infection [6].
• The immunology of the 65 kd heat shock protein (hsp65) is paradoxical [6].
• S. typhimurium-stimulated cytotoxic T lymphocytes recognizing the GroEL epitope cross-reacted with a peptide derived from mouse heat shock protein 60 and recognized stressed macrophages [7].
• When mice were injected with plasmid DNA encoding a single mycobacterial antigen (65-kDa heat shock protein, hsp65) they made specific cellular and humoral responses to the protein and became immune to subsequent challenge with Mycobacterium tuberculosis [8].

Chemical compound and disease context of Hspd1

• Recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing green fluorescent protein (rBCG-GFP), driven by the mycobacterial heat shock protein 70 (HSP 70) promoter from an autonomously replicating plasmid, was genetically engineered to co-express mouse interleukin-2 (IL-2) by introduction of an independent HSP 60 promoter [9].
• Murine peritoneal macrophages, maintained in serum-free conditions for 48 hours after harvesting, were incubated with C pneumoniae, chlamydial HSP 60, human HSP 60, or Escherichia coli lipopolysaccharide (LPS) [10].
• The hsp60 peptide p277 arrests the autoimmune diabetes induced by the toxin streptozotocin [11].
• The present studies were done to learn whether defined peptides of hsp60 could function as T cell carrier epitopes for a poorly immunogenic T-independent capsular polysaccharide, the Vi Ag of Salmonella typhi [12].
• Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection [13].

Biological context of Hspd1

• Our results extend the role of specific hsp60 immunomodulation in the control of beta cell autoimmunity and demonstrate that immunoregulatory networks activated by specific phsp60 vaccination can spread to other Ags targeted during the progression of diabetes, like insulin and GAD [14].
• Heat shock protein 10 (Hsp10) and heat shock protein 60 (Hsp60) were originally described as essential mitochondrial proteins involved in protein folding [15].
• One pathogenic mechanism that may explain this association is the induction of autoimmune responses to self hsp60, since these two proteins share a high degree of amino acid sequence identity [2].
• In contrast, "effector" T cells, undergoing secondary stimulation, displayed almost unchanged activation kinetics in the presence of Hsp60 [16].
• The presence of Hsp60 induces IFN-gamma and up-regulation of CD69 in T cell/PEC cocultures even in the absence of antigenic peptide and this induction of IFN-gamma is strictly dependent on the ability of the macrophages to produce IL-12 [16].

Anatomical context of Hspd1

• These results provide a molecular explanation for the effects of HSP60 treatment on T cell inflammation via innate regulation of the inflammatory response [17].
• Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway [1].
• Human heat shock protein 60 (hsp60) elicits a potent proinflammatory response in cells of the innate immune system and therefore has been proposed as a danger signal of stressed or damaged cells [18].
• Depletion of both subpopulations after Hsp60 vaccination resulted in a failure to control a lethal infection and a higher fungal burden in lungs and spleens [19].
• In testicular sections, both HSPD1 and TRA1 were closely associated with the mitochondria of spermatogonia and primary spermatocytes [20].

Associations of Hspd1 with chemical compounds

• DNA vaccination with heat shock protein 60 inhibits cyclophosphamide-accelerated diabetes [14].
• Lipopolysaccharide-free heat shock protein 60 activates T cells [21].
• Brefeldin A, a known inhibitor of MHC class I processing, interfered with lysis of IFN-gamma-stressed, but not of hsp60 peptide-pulsed, beta 2-m-/- macrophages [22].
• As model antigens, we selected the M. tuberculosis Apa (for alanine-proline-rich antigen) and the immunodominant Hsp65 and Hsp70 mycobacterial antigens combined with BCG [23].
• Synthetic peptides representing 9-mer to 11-mer aa sequences of the murine hsp60 with asparagine in anchor position 4 or 5 as the minimal requirement for H-2Db binding were tested in CTL assays [24].

Physical interactions of Hspd1

• Bacterial and host factors involved in the major histocompatibility complex class Ib-restricted presentation of Salmonella Hsp 60: novel pathway [5].
• Synaptophysin-containing microvesicles transport heat-shock protein hsp60 in insulin-secreting beta cells [25].

Regulatory relationships of Hspd1

• Yet, HSP60 can also down-regulate experimental immune arthritis and diabetes models by specific inhibition of Th1-like responses [17].
• Genes encoding IL-2 were inserted into an Escherichia coli-BCG shuttle plasmid under the control of the BCG HSP60 promoter [26].
• In time, increasing levels of hsp60-induced IL-10 could be detected in NOD mice, but not in age- and MHC class II-matched BiozziABH mice, which lack any sign of pancreatic inflammation [27].
• Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta-cell antigens [28].
• On the other hand, while production of IL-12 was observed in mice immunized with pACB/hsp65 12 weeks before, the cytokine production was inhibited by in vitro secondary stimulation with M. leprae or hsp65 [29].

Other interactions of Hspd1

• Taken together, our data strongly suggest that the presence of eukaryotic mitochondrial Hsp60 allows antigen-specific IFN-gamma secretion under conditions when an antigenic stimulus alone is not sufficient to activate T cells [16].
• Autoimmunity to heat shock protein 60 and antigen-specific production of interleukin-10 [2].
• Expression of HSP32, HSP60, HSP70, HSP84, HSP86 and heat shock cognate protein (HSC)70 mRNAs was examined by in situ hybridization [30].
• This was associated with an increase in Tlr4 expression and EDA and Hsp60 mRNA levels [31].
• Heat shock proteins as "danger signals": eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-gamma production in T cells [16].

Analytical, diagnostic and therapeutic context of Hspd1

• By Western blot, these antisera reacted with the mycobacterial Hsp65 and recognized a protein of approximately 65 kDa in P. yoelii sporozoites and P. falciparum blood stages [32].
• Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces protection in mice against Leishmania (Leishmania) major infection [3].
• By flow cytometry, we could demonstrate for the first time that hsp60 binding to macrophages occurred at submicromolar concentrations, is saturable, and can be competed by unlabeled hsp60, but not by unrelated proteins, thus confirming the classic characteristics of specific ligand-receptor interactions [33].
• Immuno-electron microscopy technique was employed to investigate the cellular distribution of 60 kDa heat-shock protein (HSP60) in pancreatic Beta cells of control and non-obese diabetic mice [34].
• Immunoblotting revealed that lower concentrations of hsp60 are also present in normal mouse joints, and that the level of expression increases with age, in parallel with greater susceptibility to PIA [35].

References