scholarly journals Could the Heat Shock Proteins 70 Family Members Exacerbate the Immune Response in Multiple Sclerosis? An in Silico Study

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 615 ◽  
Author(s):  
Luigi Chiricosta ◽  
Agnese Gugliandolo ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Heat Shock ◽  
Corpus Callosum ◽  
In Silico ◽  
Internal Capsule ◽  
Optic Chiasm ◽  
Brain Areas ◽  
In Silico Study ◽  
Shock Proteins

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. It represents one of the main causes of neurological disability in young people. In MS, the autoimmune response is directed against myelin antigens but other possible bio-molecular markers are investigated. The aim of this work was, through an in silico study, the evaluation of the transcriptional modifications between healthy subjects and MS patients in six brain areas (corpus callosum, hippocampus, internal capsule, optic chiasm, frontal and parietal cortex) in order to identify genes representative of the disease. Our results show the upregulation of the Heat Shock Proteins (HSPs) HSPA1A, HSPA1B, HSPA7, HSPA6, HSPH1 and HSPA4L of the HSP70 family, among which HSPA1A and HSPA1B are upregulated in all the brain areas. HSP70s are molecular chaperones indispensable for protein folding, recently associated with immune system maintenance. The little overexpression of the HSPs protects the cells from stress but extreme upregulation can contribute to the MS pathogenesis. We also investigated the genes involved in the immune system that result in overall upregulation in the corpus callosum, hippocampus, internal capsule, optic chiasm and are absent in the cortex. Interestingly, the genes of the immune system and the HSP70s have comparable levels of expression.

Heat-shock proteins as activators of the innate immune system

2002 ◽  
Vol 23 (3) ◽  
pp. 130-135 ◽  
Author(s):  
Robert P.A Wallin ◽  
Andreas Lundqvist ◽  
Solveig H Moré ◽  
Arne von Bonin ◽  
Rolf Kiessling ◽  
...  
Keyword(s):  
Immune System ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Innate Immune System ◽  
Innate Immune ◽  
Shock Proteins

Heat Shock Proteins in Multiple Sclerosis

2009 ◽  
pp. 101-111 ◽  
Author(s):  
Celia F. Brosnan ◽  
Luca Battistini ◽  
Krzysztof Selmaj
Keyword(s):  
Multiple Sclerosis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Shock Proteins

CD40 Ligand Stimulation of Multiple Myeloma Cells Results in Upregulation of Surface Expressed Heat Shock Proteins and Increased Antigenicity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3351-3351
Author(s):  
Charles A. Gullo ◽  
William Hwang ◽  
Melvin Au ◽  
Edward A. Greenfield ◽  
Kenneth C. Anderson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Heat Shock ◽  
Cell Membrane ◽  
Heat Shock Proteins ◽  
Flow Cytometric Analysis ◽  
Cd40 Ligand ◽  
Flow Cytometric ◽  
Shock Proteins ◽  
Stimulation Of

Abstract Effective immune-based therapies against the plasma cell malignancy, multiple myeloma (MM), are currently lacking. Identification of novel antigens (Ag) on the surface of MM cells to use as cellular targets for the destruction of cancer cells by the body’s immune system has been of great interest. We and others have demonstrated that CD40 stimulation of MM cells results in marked upregulation of membrane bound proteins such as Ku86. Using CD40 triggered MM cells as immunogens and hybridoma technology; we generated a monoclonal antibody (mAb), 6D11, that recognizes a CD40 induced cell membrane Ag on MM cells. This Ag is detectable on the surface of MM cells using indirect immunofluorescence flow cytometric analysis. Moreover, in Western immunoblotting assays, 6D11 mAb reacts with a 94 kDa protein, which is strongly associated with a 78 kDa protein. Using high performance liquid chromatography and protein microsequencing, we confirm that these proteins are the heat shock proteins (HSP), glucose-regulated peptide 94 (GRP94) and GRP78, respectively. These data were confirmed using co-immunprecipitation experiments. Furthermore, we demonstrate through indirect immunofluorescence flow cytometric analysis and quantitative real time reverse transcription polymerase chain reaction (RQ-PCR) that CD40 ligand (CD40L) stimulation of MM cells results in rapid upregulation of both GRP94 and GRP78. Since HSPs have been shown to play a role in both Ag presentation, as well as the intracellular transport of cellular Ags, it is tempting to speculate that cell membrane expression of tumor-specific peptides could also be induced via CD40 triggering. Accordingly, CD40 induced cell membrane HSP expression resulted in increased antigenicity as determined by increased co-stimulatory molecule expression on Ag presenting cells (APC) and by increased immunoreactivity in mixed lymphocyte reactions (MLR). This suggests that CD40 induced HSP expression may indeed result in increased recognition of MM cancer by the immune system. Our study therefore supports the development of CD40-based targeted cell therapies against MM.

T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis

1992 ◽  
Vol 5 (6) ◽  
pp. 691-702 ◽  
Author(s):  
Marco Salvetti ◽  
Carla Buttinelli ◽  
Giovanni Ristori ◽  
Maurizio Carbonari ◽  
Michela Cherchi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
T Lymphocyte ◽  
Shock Proteins ◽  
Lymphocyte Reactivity

Heat-shock proteins and autoimmunity: Implications for multiple sclerosis

1993 ◽  
Vol 34 (1) ◽  
pp. 5-7 ◽  
Author(s):  
Richard M. Runsohoff ◽  
Richard A. Rudich
Keyword(s):  
Multiple Sclerosis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Shock Proteins

Expression of heat shock proteins 27 and 72 correlates with specific commensal microbes in different regions of porcine gastrointestinal tract

2014 ◽  
Vol 306 (12) ◽  
pp. G1033-G1041 ◽  
Author(s):  
Hao-Yu Liu ◽  
Johan Dicksved ◽  
Torbjörn Lundh ◽  
Jan Erik Lindberg
Keyword(s):  
Immune System ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Bacterial Species ◽  
Host Immune System ◽  
Gi Tract ◽  
Microbe Interactions ◽  
Cell Type Specific ◽  
Host Microbe Interactions ◽  
Shock Proteins

The gastrointestinal (GI) tract of mammals is inhabited by trillions of microorganisms, resulting in exceedingly complex networking. The interaction between distinct bacterial species and the host immune system is essential in maintaining homeostasis in the gut ecosystem. For instance, the gut commensal microbiota dictates intestinal mucosa maturation and its abundant immune components, such as cytoprotective heat shock proteins (HSP). Here we examined physiological expression of HSP in the normal porcine GI tract and found it to be gut region- and cell type-specific in response to dietary components, microbes, and microbial metabolites to which the mucosa surface is exposed. Correlations between HSP72 expression and ileal Lactobacillus spp. and colonic clostridia species, and between HSP27 expression and uronic acid ingestion, were important interplays identified here. Thus this study provides novel insights into host-microbe interactions shaping the immune system that are modifiable by dietary regime.

Microsurgical anatomy of the distal anterior cerebral artery

1978 ◽  
Vol 49 (2) ◽  
pp. 204-228 ◽  
Author(s):  
David Perlmutter ◽  
Albert L. Rhoton
Keyword(s):  
Corpus Callosum ◽  
Cerebral Artery ◽  
Anterior Cerebral Artery ◽  
Internal Capsule ◽  
Optic Chiasm ◽  
Anterior Communicating Artery ◽  
Microsurgical Anatomy ◽  
Content Type ◽  
Cm Points ◽  
Distal Anterior Cerebral Artery

✓ The microsurgical anatomy of the distal anterior cerebral artery (ACA) has been defined in 50 cerebral hemispheres. The distal ACA, the portion beginning at the anterior communicating artery (ACoA), was divided into four segments (A2 through A5) according to Fischer. The distal ACA gave origin to central and cerebral branches. The central branches passed to the optic chiasm, suprachiasmatic area, and anterior forebrain below the corpus callosum. The cerebral branches were divided into cortical, subcortical, and callosal branches. The most frequent site of origin of the cortical branches was as follows: orbitofrontal and frontopolar arteries, A2; the anterior and middle internal frontal and callosomarginal arteries, A3; the paracentral artery, A4; and the superior and inferior parietal arteries, A5. The posterior internal frontal artery arose with approximately equal frequency from A3 and A4 and the callosomarginal artery. All the cortical branches arose more frequently from the pericallosal than the callosomarginal artery. Of the major cortical branches, the internal frontal and paracentral arteries arose most frequently from the callosomarginal artery. The distal ACA of one hemisphere sent branches to the contralateral hemisphere in 64% of brains. The anterior portions of the hemisphere between the 5-cm and 15-cm points on the circumferential line showed the most promise of revealing a recipient artery of sufficient size for an extracranial-intracranial artery anastomosis. The distal ACA was the principal artery supplying the corpus callosum. The recurrent artery, which arose from the A2 segment in 78% of hemispheres, sent branches into the subcortical area around the anterior limb of the internal capsule.

scholarly journals Exposure to Mycobacteria Primes the Immune System for Evolutionarily Diverse Heat Shock Proteins

2005 ◽  
Vol 73 (11) ◽  
pp. 7687-7696 ◽  
Author(s):  
Khaleda Rahman Qazi ◽  
Mousumi Rahman Qazi ◽  
Esther Julián ◽  
Mahavir Singh ◽  
Manuchehr Abedi-Valugerdi ◽  
...  
Keyword(s):  
Immune System ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Chlamydia Pneumoniae ◽  
Effective Vaccine ◽  
Interferon Production ◽  
Vaccine Adjuvants ◽  
Mycobacterium Vaccae ◽  
Shock Proteins ◽  
High Degree

ABSTRACT During stress conditions, such as infection, the synthesis of heat shock proteins (HSPs) in microorganisms is upregulated. Since a high degree of homology exists within each HSP family, we postulated that exposure to microorganisms could prime the immune system for evolutionarily diverse HSPs. We tested this hypothesis by priming mice with three microorganisms, namely, Mycobacterium bovis BCG, Mycobacterium vaccae, and Chlamydia pneumoniae. After this, mice received a dose of the various HSPs. We found that BCG and M. vaccae but not C. pneumoniae primed the immune system for the induction of secondary immunoglobulin G (IgG) responses to most of the HSPs tested. Analysis of the IgG1 and IgG2a profile and gamma interferon production induced against the HSPs revealed the induction of a mixture of responses. We also observed that sera from mice treated with M. vaccae and HSP70 were cross-reactive, but no antibody complexes were observed in their kidneys, which frequently are targets for autoantibody reactions. Our findings add further support for the use of HSPs as effective vaccine adjuvants.

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