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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

Πλατή, Ιωάννα

Thesis advisor

Βενυχάκη, Μαρία

Reviewer

Μπριασούλης, Γεώργιος
Καμπά, Μαρία-Ελένη
Δημητρίου, Ελένη
Ηλία, Σταυρούλα
Χαραλαμπόπουλος, Ιωάννης

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.

Language

Greek

Subject

Citokines

Corticosterone

Glutamine

Γλουταμίνη

Κορτικοστερόνη

Κυτοκίνες

Πρωτεϊνη θερμικής καταπληξίας 70

Issue date

2023-04-05