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Identifier |
000453546 |
Title |
Μελέτη του ρόλου της έλλειψης της HSP70 στη φλεγμονώδη απόκριση in vivo και in vitro |
Alternative Title |
Evaluation of the role of HSP70 deficiency in the inflammatory response in vivo and in vitro |
Author
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Πλατή, Ιωάννα
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Thesis advisor
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Βενυχάκη, Μαρία
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Reviewer
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Μπριασούλης, Γεώργιος
Καμπά, Μαρία-Ελένη
Δημητρίου, Ελένη
Ηλία, Σταυρούλα
Χαραλαμπόπουλος, Ιωάννης
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Abstract |
Heat Shock proteins (HSPs), especially the 70-kDa heat shock protein (HSP70),
are a family of highly conserved proteins, also known as “stress response proteins”,
involved in the basic mechanisms of cellular protection and play key role in the
regulation of the immune response. HSP expression is highly induced by different types
of agents and catabolic stimuli, such as oxidative, thermal and metabolic stresses as
well as, infection, inflammation and intense exercise.Glutamine (GLN) has been shown
to play a protective role against inflammatory injury and illness in experimental and
clinical settings. Several studies have suggested a bidirectional relationship between
GLN-mediated protection and enhanced HSP70, but the exact mechanism is not fully
understood yet.
The aim of the present study was to explore the mechanism through which
HSP70 is involved in systemic inflammation and the role of GLN as part of this
mechanism. For this purpose, we utilized mice with specific deletion of the Hsp70.1
and Hsp70.3 genes for the in vivo studies and primary macrophages were collected from
Hsp70+/+ and Hsp70-/-for the in vitro studies. Macrophages play an essential role in
inflammation and host defense, regulating the immune response and maintaining tissue
homeostasis. Thus, we investigate the role of HSP70 in LPS-induced systemic
inflammation both in vivo and in vitro.
Our study provides clear evidence that HSP70 deficiency is associated with
lower cytokine levels in plasma and lung tissue. On the contrary, HSP70 gene deletion
leads to an increased inflammatory response by peritoneal murine macrophages from
Hsp70-/- mice, which produced significantly increased levels of TNF-α, IL-6 and IL-8
compared with Hsp70 +/+ mice-derived macrophages, after LPS stimulation.
In conclusion, this phD thesis showed that the absence of HSP70 is associated
in vivo with a reduced inflammatory response, while in vitro, the lack of HSP70 is
associated with a pro-inflammatory phenotype. Our data suggest that the reduced
inflammatory response observed in the absence of HSP70 in vivo is likely dependent
on the anti-inflammatory action of glucocorticosteroids. Furthermore, HSP70 may not
play a significant role in attenuating the inflammatory response after GLN
administration in LPS-induced inflammation, suggesting alternatives pathways that
bypass the innate immune response. Alternatively, in the absence of HSP70, HSP90
expression may be necessary for the development of an inflammatory response. Thus measuring HSP90 levels in macrophages may be a potential marker for the
inflammatory response.
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Language |
Greek |
Subject |
Citokines |
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Corticosterone |
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Glutamine |
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Γλουταμίνη |
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Κορτικοστερόνη |
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Κυτοκίνες |
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Πρωτεϊνη θερμικής καταπληξίας 70 |
Issue date |
2023-04-05 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/d/5/0/metadata-dlib-1675245282-383290-12022.tkl
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Views |
734 |