Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Healthy individuals manifest natural T cell reactivity to epitopes of the 60-kDa heat shock protein (hsp60) of both self and bacterial origin. 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. Homologous peptides were synthesized from the mouse self-hsp60 molecule (CP1m), from the closely related human hsp60 molecule (CP1h), and from the more distant Escherichia coli (CP1ec) and mycobacterial (CP1mt) hsp60 molecules. The peptides were conjugated to Vi and tested for their immunogenicity in BALB/c (H-2d) and H-2 congenic mice (H-2k and H-2b). We now report that the self-CP1m and cross-reactive CP1h peptides were as immunogenic as was the non-cross-reactive foreign CP1ec peptide. Small amounts of the CP1 peptide, even in PBS, sufficed to induce anti-Vi Abs of the IgG1 (T-dependent) isotype in naive mice. The carrier effect was associated with the ability of the peptides to bind to APC and to induce T cell proliferation. H-2d and H-2k mice, but not H-2b mice responded to CP1m/h and CP1ec. None of the mice responded to CP1mt. No signs of inflammation or autoimmune disease were detected. Thus, natural T cell autoimmunity exists and can be harnessed to provide T cell help for Ab production to a foreign bacterial molecule in a synthetic vaccine.
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PMID:Self and foreign 60-kilodalton heat shock protein T cell epitope peptides serve as immunogenic carriers for a T cell-independent sugar antigen. 753 39

The effect of AHN 086 [1-(2-isothiocyanatoethyl)-7-chloro-1,3-dihydro-5-(4- chloro-phenyl)-2H-1,4-benzodiazepine-2-one hydrochloride], an irreversible ligand of the mitochondrial benzodiazepine receptor, was studied in the heat shock protein (HSP) expression and the activation of dog neutrophils. At micromolar concentrations, AHN 086 induced a dose-dependent increase in free radical production (309 +/- 13% at 1 x 10(-5) M). This compound also increased the phagocytic activity (73 +/- 3.5% at 5 x 10(-6) M). Immunohistochemical results showed that AHN 086 induced the expression of HSP in neutrophil membranes. At 1 x 10(-5) M, the percentage of positive cells was: 90.2 (27 kD), 90.6 (72 kD) and 92.8 (90 kD). This expression was accompanied by a decrease in the presence of nuclear and cytoplasmic HSP. Flow cytometry studies showed that this cell membrane expression was located on the neutrophil surface and could be a consequence of HSP mobilization from nucleus and cytoplasm.
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PMID:Dog neutrophil stimulation and cell surface expression of heat shock proteins induced by AHN 086. 761 4

The effect of peripheral-type benzodiazepines on dog neutrophil stimulation was studied. Ro 5-4864 (a specific ligand of mitochondrial benzodiazepine receptor) and diazepam (which binds both to mitochondrial and central benzodiazepine receptors) did not show any direct toxic effect against neutrophils. PK 11195, a putative antagonist of the mitochondrial benzodiazepine receptor and an isoquinoline derivative, had a direct toxic effect at a concentration of 5 x 10(-5) M (72% of cells were viable). Ro 5-4864 (10(-6)-10(-4) M) and diazepam (10(-6)-2.5 x 10(-4) M) induced an intracellular oxidative stress in dog neutrophils. These compounds, in a micromolar range, also induced a concentration-dependent cell surface expression of heat shock protein (HSP) families. The percentages of positive cells that express these proteins were: 76.2% for HSP 27 kDa; 54.3% for HSP 72 kDa and 69.6% for HSP 90 kDa for Ro 5-4864 (10(-4) M), and 66.7% for HSP 27 kDa; 45.4% for HSP 72 kDa and 78.3 for HSP 90 kDa for diazepam (2.5 x 10(-4) M). It appears that this HSP expression, induced by peripheral-type benzodiazepines could be mediated by an intracellular oxidative stress.
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PMID:Cell surface expression of heat shock proteins in dog neutrophils induced by mitochondrial benzodiazepine receptor ligands. 777 58

Increased accumulation of collagens in extracellular matrix (ECM) is mainly responsible for bleomycin-induced pulmonary fibrosis in rats. This study was designed to assess whether increased collagen accumulation in bleomycin-induced pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular chaperone for collagen biosynthesis. We investigated the expression of type I and type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen male Wistar rats were divided into two groups; group I: bleomycin-induced pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg body weight) intratracheally. Three bleomycin-treated rats and two age-matched control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of the experiment. In bleomycin-treated rats, histological examination revealed pulmonary fibrosis, which increased with time. Increased type I and type III collagen desposition was observed in the lungs of all the bleomycin-treated rats. Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In addition, increased numbers of phenotypically altered myofibroblasts (alpha-smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of collagens and their molecular chaperone HSP47 expression was found in the bleomycin-treated lungs, and their co-localization could be detected by double immunostaining. Overexpression of HSP47 may play a significant part in the excessive assembly of collagens and could contribute in this way to the fibrosis found in bleomycin-treated rat lungs.
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PMID:Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47. 964 46

We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-alpha) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858-R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D-gal) was used to selectively inhibit liver protein synthesis. D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 microg/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10--18 h post-LPS. A significant increase of serum TNF-alpha accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS.
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PMID:Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats. 1120 60

Neisseria meningitidis type B is a major world-health problem. The Meningococcus type B capsular polysaccharide (MnB) is very poorly immunogenic and no vaccine to the antigen exists. Here, we conjugated the MnB to a T-cell carrier peptide (p458) derived from the self-60kDa heat shock protein molecule. The conjugate vaccine was effective in inducing long-lasting IgG antibodies to the MnB antigen in mice. The vaccine was also immunogenic when injected in PBS. Thus, the p458 carrier peptide can induce T-cell help for the switch to IgG Ab to the MnB antigen.
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PMID:A conjugate vaccine composed of a heat shock protein 60 T-cell epitope peptide (p458) and Neisseria meningitidis type B capsular polysaccharide. 1684 73

Previously, we reported that a peptide, p458, from the sequence of the mammalian 60-kDa heat shock protein (hsp60) molecule can serve as a carrier in conjugate vaccines with capsular polysaccharide (CPS) molecules of various bacteria. These conjugate vaccines were effective injected in PBS without added adjuvants. We now report that p458 conjugated to pneumococcal CPS type 4 (PS4) manifests innate adjuvant effects: it stimulated mouse macrophages to secrete IL-12 and induced the late appearance of PS4 on the macrophage surface in a TLR4-dependent manner; PS4 alone or conjugated to other carriers did not stimulate macrophages in vitro. The injection of macrophages manifesting PS4 on the surface into mice induced long-term resistance to lethal Streptococcus pneumoniae challenge. The TLR4 ligand LPS could also induce the late appearance on the surface of unconjugated PS4 and resistance to challenge in injected mice. Resistance was not induced by macrophages containing only internalized PS4 or by pulsed macrophages that had been lysed. Glutaraldehyde-fixed macrophages pulsed with PS4 did induce resistance to lethal challenge. Moreover, bone marrow-derived dendritic cells activated by LPS and pulsed with unconjugated CPS were also effective in inducing resistance to lethal challenge. Resistance induced by the PS4-pulsed bone marrow-derived dendritic cell was specific for pneumococcal CPS serotypes (type 3 or type 4) and was associated with the induction of CPS-specific IgG and IgM Abs.
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PMID:Pneumococcal capsular polysaccharide is immunogenic when present on the surface of macrophages and dendritic cells: TLR4 signaling induced by a conjugate vaccine or by lipopolysaccharide is conducive. 1825 Apr 50

Rhodococcus equi remains a significant bacterial pathogen, causing severe pyogranulomatous pneumonia in foals aged 1-3 months. There is no effective vaccine currently available for the prevention of R. equi pneumonia. DNA vaccines are known to offer specific advantages over conventional vaccines. The aim of this study was to demonstrate efficacy of our recombinant DNA vaccine candidates, namely pcDNA3-Re1, pcDNA3-Re3 and pcDNA3-Re5 by combining a heat shock protein GroEL2 to a virulence-associated protein A (VapA) from R. equi to protect C3H/He mice against the R. equi infection. VapA was shown to be strongly recognised by sera from pneumonic foals. All vaccines elicited at least a doubling of the IgG2a/IgG1 ratio in comparison to the controls, indicating a bias to the Th1 response, which is postulated to be crucial for bacterial clearance and protective immunity against intracellular pathogens including R. equi. In addition, the immunised mice showed a significant reduction in R. equi in their lungs at 7 days after the aerosol challenge in comparison to PBS treated mice. However, examination of lung pathology 14 days after the challenge showed no gross differences in pathological changes between the unvaccinated and vaccinated animals. The lack of significant pathological changes suggests that the precise level of protection against R. equi pneumonia in the murine model of infection may not represent a true effectiveness of the potential vaccine candidates, indicating the mouse may not be the ideal non-equine model for vaccine studies and (or) the incomplete immunogenic antigen of vapA-based DNA vaccine constructs that mount an inadequate cell-mediated immune response against the R. equi infection.
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PMID:Chimeric vapA/groEL2 DNA vaccines enhance clearance of Rhodococcus equi in aerosol challenged C3H/He mice. 1842 49

The aim of this study was to investigate the effect of heat shock protein-70 (HSP-70) on splenocyte proliferation and nitric oxide (NO) production in the BALB/c mice fibrosarcoma tumor model. To do so, HSP-70 was induced in the lysate of heat-shocked tumor cells and WEHI-164 cells (mouse fibrosarcoma cell line) were injected subcutaneously into the right flank of inbred BALB/c mice to establish a tumor model. Three animal bearing tumor groups were applied: the test group; vaccinated with HSP-70 enriched tumor lysate; control group I, vaccinated with tumor lysate only; and control group II, which received PBS. Using immunoblot analysis, an increase of HSP-70 expression was detected in the lysate of heat-shocked cells in comparison with non-heat-shocked cells. The effect of the test lysate on NO production was measured both in vitro and in vivo in the peritoneal macrophages and splenocytes of tumor bearing mice, respectively. The result showed a significant increase in NO production both in vitro by peritoneal macrophages and in vivo after immunization with HSP-70 enriched tumor lysate. In addition, tumor growth was significantly postponed and the proliferation of splenocytes was increased in the test group. Our results indicate that the lysate of heat-shocked tumor cells was more potent than that of non-heat-shocked tumor cells in inducing anti-tumor immunity. Since production of NO by HSP-activated antigen presenting cells (APCs) is likely to affect innate immunity and tumor growth, the probable mechanism of postponing tumor growth would be NO production by innate immune cells. These findings provide a useful therapeutic model for developing novel approaches to cancer treatments.
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PMID:The effect of vaccination with the lysate of heat-shocked tumor cells on nitric oxide production in BALB/c mice with fibrosarcoma tumor. 1845 32

Evidence have indicated the impairment of central nervous system (CNS) and neuropsychiatric disorder in patients with systemic lupus erythematosus (SLE). However, little is known to improve the brain abnormality in SLE. To investigate the effect of cystamine on brain abnormality in SLE, NZB/W F1 mice were used as the animal model. Notably, significantly reduced neural Nitric Oxide Synthase (nNOS), inducible Nitric Oxide Synthase (iNOS), p53, p21(WAF1/CIP1), and heat shock protein (HSP)-90 proteins were detected in the brain of NZB/W F1 mice that were treated with cystamine. In contrast, no variation was observed between the brain samples of BALB/c mice that were treated with PBS or cystamine. Moreover, significantly reduced Toll-like receptors- (TLR-) 4, 5 and 7 were detected in the brain samples of NZB/W F1 mice that were treated with cystamine whereas no variation of TLR-4, TLR-5, TLR-7, and TLR-9 was observed in BALB/c mice that were treated with PBS or cystamine. These findings demonstrated the beneficial effects of cystamine on brain abnormality in NZB/W F1 mice and probably suggested the potential of cystamine on treating patients with neuropsychiatric SLE.
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PMID:Cystamine attenuates the expressions of NOS- and TLR-associated molecules in the brain of NZB/W F1 mice. 1926 57


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