scholarly journals The Autoantigenic Proinsulin B-Chain Peptide B11-23 Synergises with the 70 kDa Heat Shock Protein DnaK in Macrophage Stimulation

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Elias Blasius ◽  
Elke Gülden ◽  
Hubert Kolb ◽  
Christiane Habich ◽  
Volker Burkart
Keyword(s):  
Heat Shock ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
The Core ◽  
Hsp70 Family ◽  
Macrophage Stimulation ◽  
Shock Proteins ◽  
Autoimmune Reactivity ◽  
Necrosis Factor

Background. Heat shock proteins (Hsp) act as intracellular chaperones and in addition are used as adjuvant in vaccines of peptides complexed with recombinant Hsp. By interacting with autologous peptides, Hsp may promote the induction of autoimmune reactivity. Objective. Here, we analysed whether the effect of Hsp on macrophages is modulated by insulin peptides known to interact with Hsp. Results. Combinations of the 70 kDa Hsp DnaK with peptide B11-23 from the core region of the proinsulin B-chain induced the release of the inflammatory mediators interleukin-6, tumor necrosis factor α, and interleukin-1β from cells of human and murine macrophage lines. In parallel, there was high-affinity binding of B11-23 to DnaK. DnaK mixed with peptides from other regions of the insulin molecule did not stimulate cytokine secretion. DnaK alone induced little cytokine production, and peptides alone induced none. Conclusion. The macrophage-stimulating potential of Hsp70 family proteins when combined with the proinsulin B-chain peptide B11-23 may contribute to the immunodominance of this peptide in the development of beta cell-directed autoimmunity in type 1 diabetes.

Herpes simplex virus type 2 UL14 gene product has heat shock protein(HSP)-like functions

2002 ◽  
Vol 115 (12) ◽  
pp. 2517-2527
Author(s):  
Yohei Yamauchi ◽  
Kaoru Wada ◽  
Fumi Goshima ◽  
Tohru Daikoku ◽  
Kenzo Ohtsuka ◽  
...  
Keyword(s):  
Heat Shock ◽  
Nuclear Translocation ◽  
Osmotic Shock ◽  
Minor Component ◽  
Firefly Luciferase ◽  
Hsp70 Family ◽  
Arginine Residues ◽  
Simplex Virus ◽  
A Minor ◽  
Shock Proteins

The HSV-2 UL14 gene encodes a 32 kDa protein that is a minor component of the viral tegument. The protein relocates other viral proteins such as VP26 and UL33 protein into the nuclei of transiently coexpressing cells(Yamauchi et al., 2001). We found that the protein shared some characteristics of heat shock proteins(HSPs) or molecular chaperones, such as nuclear translocation upon heat shock,ATP deprivation and osmotic shock. Interestingly, a significant homology over a stretch of 15 amino acids was found between an N-terminal region of HSV UL14 protein and the substrate-binding domain of Hsp70 family proteins. Two arginine residues in this region were important for nuclear translocation of VP26. In addition, overexpression of UL14 protein increased the activity of coexpressed firefly luciferase, which suggested that the protein functioned in the folding of newly synthesized luciferase. We thus conclude that UL14 protein can act as a chaperone-like protein in a singly expressed state.

scholarly journals Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0161505 ◽  
Author(s):  
Ilgiz A. Mufazalov ◽  
Tommy Regen ◽  
Carsten Schelmbauer ◽  
Janina Kuschmann ◽  
Alisa M. Muratova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Receptor Type ◽  
Intrinsic Defects ◽  
Knock Out ◽  
Knock Out Mouse

scholarly journals HLA associations in clozapine-induced agranulocytosis

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1177-1183 ◽  
Author(s):  
JJ Yunis ◽  
D Corzo ◽  
M Salazar ◽  
JA Lieberman ◽  
A Howard ◽  
...  
Keyword(s):  
Heat Shock ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Clinical Status ◽  
Ashkenazi Jewish ◽  
Major Histocompatability Complex ◽  
Jewish Ancestry ◽  
Hla Dr ◽  
Shock Proteins ◽  
Necrosis Factor

Abstract We previously reported preliminary results of association of clozapine- induced agranulocytosis (CA) with HLA-B38, DR4, DQ3 in five Ashkenazi Jewish patients and with HLA-DR2, DQ1 in four non-Jewish patients. In the present study, 31 additional patients with CA, 10 Ashkenazi Jewish, and 21 of non-Jewish ancestry, were studied. HLA alleles and haplotypes were compared among 52 patients (33 Ashkenazi Jewish, 19 non-Jewish) matched for ethnic background and clinical status. Our results show two associations and define the HLA allele markers for the Ashkenazi Jewish and non-Jewish haplotypes associated with CA. The most important markers for susceptibility for CA in Ashkenazi Jewish patients were DRB1*0402, DQB1*0302, and DQA1*0301, and in non-Jewish patients, HLA- DR*02, DQB1*0502, and DQA1*0102. HLA-DRB1*011 and DQB1*0301 were underrepresented in Ashkenazi Jewish patients when compared with controls. We hypothesize that genes of the major histocompatability complex, other than class I and class II, are responsible for CA; among them are the variants of the heat-shock proteins 70 or the tumor necrosis factor loci.

Colchicine has opposite effects on interleukin-1 beta and tumor necrosis factor-alpha production

1991 ◽  
Vol 261 (4) ◽  
pp. L315-L321 ◽  
Author(s):  
J. N. Allen ◽  
D. J. Herzyk ◽  
M. D. Wewers
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

To study the role of microtubules in cytokine production, the effect of the microtubule depolymerizing agent colchicine on lipopolysaccharide endotoxin (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) release by blood monocytes and alveolar macrophages were examined. Immunofluorescence microscopy demonstrated that LPS resulted in the appearance of microtubule-containing cytoplasmic appendages and that colchicine, which resulted in microtubule disruption in monocytes, blocked appendage formation. Colchicine resulted in approximately 50% increase in LPS-induced IL-1 beta release and a 50% decrease in LPS-induced TNF-alpha release by human monocytes at all doses of LPS tested. Although colchicine resulted in a statistically significant increase in LPS-stimulated human alveolar macrophage IL-1 beta release, the increase was not as great as that observed with monocytes. Northern blot analysis suggested that the colchicine effect occurs pretranslationally because colchicine caused an increase in LPS-stimulated IL-1 beta mRNA levels and a decrease in TNF-alpha mRNA levels. These results suggest that microtubules contribute to the regulation of endotoxin-stimulated mononuclear phagocyte cytokine production and that this regulation differs significantly between IL-1 beta and TNF-alpha.

scholarly journals Pediatric Sepsis: Genetic Considerations

2017 ◽  
Vol 07 (01) ◽  
pp. e76-e88 ◽  
Author(s):  
N. Elek ◽  
S. Sandor ◽  
G. Balazs ◽  
P. Dahlem
Keyword(s):  
Interleukin 1 ◽  
Genetic Alterations ◽  
Coagulation Cascade ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mannose Binding ◽  
Pediatric Sepsis ◽  
Factor Α ◽  
Shock Proteins ◽  
Necrosis Factor

AbstractThe mortality of childhood sepsis continues to be rather high. When it comes to prevention and adequate therapy, individual differences and genetic alterations are becoming more and more important. These may affect molecules involved in pathogen recognition (e.g., lipopolysaccharide-binding protein, mannose-binding lectin, bactericidal/permeability-increasing protein, Toll-like receptors), signal transduction pathways (e.g., cRel), proinflammatory (e.g., tumor necrosis factor-α, interleukin-1 [IL-1], IL-6, IL-8) as well as anti-inflammatory cytokines (e.g., IL-4, IL-10, IL-1 receptor antagonist), members of the coagulation cascade, and other molecules active in the process of systemic inflammatory response syndrome (e.g., heat shock proteins, complement system). The most common genetic polymorphisms are the so-called single-nucleotide polymorphisms, which entail the change of a single base. Genetic mutations have an impact on susceptibility, severity, and outcome of sepsis. Understanding such mutations may improve treatment efficiency; although there is a considerably limited choice of causal treatments today, they may become available upon future developments in genetic therapy.

Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins

Science ◽  
1992 ◽  
Vol 258 (5081) ◽  
pp. 484-486 ◽  
Author(s):  
S. Nadler ◽  
M. Tepper ◽  
B Schacter ◽  
C. Mazzucco
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Hsp70 Family ◽  
Shock Proteins

scholarly journals Oligomerization of ICP4 and Rearrangement of Heat Shock Proteins May Be Important for Herpes Simplex Virus Type 1 Prereplicative Site Formation

2008 ◽  
Vol 82 (13) ◽  
pp. 6324-6336 ◽  
Author(s):  
Christine M. Livingston ◽  
Neal A. DeLuca ◽  
Dianna E. Wilkinson ◽  
Sandra K. Weller
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Heat Shock ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Site Formation ◽  
Nucleoprotein Complexes ◽  
Simplex Virus ◽  
Shock Proteins

ABSTRACT Herpes simplex virus type 1 (HSV-1) DNA replication occurs in replication compartments that form in the nucleus by an ordered process involving a series of protein scaffold intermediates. Following entry of viral genomes into the nucleus, nucleoprotein complexes containing ICP4 can be detected at a position adjacent to nuclear domain 10 (ND10)-like bodies. ND10s are then disrupted by the viral E3 ubiquitin ligase ICP0. We have previously reported that after the dissociation of ND10-like bodies, ICP8 could be observed in a diffuse staining pattern; however, using more sensitive staining methods, we now report that in addition to diffuse staining, ICP8 can be detected in tiny foci adjacent to ICP4 foci. ICP8 microfoci contain UL9 and components of the helicase-primase complex. HSV infection also results in the reorganization of the heat shock cognate protein 70 (Hsc70) and the 20S proteasome into virus-induced chaperone-enriched (VICE) domains. In this report we show that VICE domains are distinct but adjacent to the ICP4 nucleoprotein complexes and the ICP8 microfoci. In cells infected with an ICP4 mutant virus encoding a mutant protein that cannot oligomerize on DNA, ICP8 microfoci are not detected; however, VICE domains could still be formed. These results suggest that oligomerization of ICP4 on viral DNA may be essential for the formation of ICP8 microfoci but not for the reorganization of host cell chaperones into VICE domains.

scholarly journals Interleukin 1 induces the expression of a heat-shock gene in chondrocytes

1991 ◽  
Vol 277 (2) ◽  
pp. 327-330 ◽  
Author(s):  
T F Cruz ◽  
R A Kandel ◽  
I R Brown
Keyword(s):  
Heat Shock ◽  
Interleukin 1 ◽  
Heat Shock Gene ◽  
Proteoglycan Synthesis ◽  
Hsp70 Mrna ◽  
Mrna Species ◽  
Shock Gene ◽  
Shock Proteins ◽  
Arthritic Joints

The presence of T cells and antibodies reactive with heat-shock proteins (hsps) in the joints of patients with rheumatoid arthritis may indicate a role of hsps in this disease. In the present study we examined whether increased temperature and interleukin 1 (IL 1), both of which are elevated in arthritic joints, induced the expression of two hsp70 genes in bovine chondrocyte cultures. We found that heat shock resulted in increased expression of constitutive and inducible hsp70 mRNA species. IL 1 and phorbol 12-myristate 13-acetate (PMA) also induced an increase in the constitutive hsp70 mRNA species, but without affecting the expression of the inducible hsp70 gene. The increase induced by IL 1 was observed only after 3 h, whereas increases induced by PMA were observed within 1 h. For all treatments, the hsp70 mRNA decreased by 24 h. Heat treatment of chondrocytes did not affect levels of collagenase and caseinase activity in the medium, nor did it alter proteoglycan synthesis by these cells.

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