Obiekt
Tytuł: Molecular mechanisms of activation of endothelial cells of the cardiac muscle by autoreactive CD4+ T lymphocytes and the involvement of TNF-α in the course of autoimmune myocarditis
Abstrakt:
Autoimmune myocarditis is a condition characterized by inflammation of the heart muscle due to an autoimmune response, often resulting in severe cardiac dysfunction. This work aims to shed light on the complex role of TNF-α in the course of myocarditis, with a specific focus on the biology of autoreactive T lymphocytes and cardiac microvascular endothelial cells. Using inducible and genetic models of autoimmune myocarditis, the study reveals that TNF-α knockout can lead to divergent outcomes. While some mice lacking TNF-α are protected from disease development, others experience severe myocarditis. The contrasting outcomes in TNF-α deficient mice may be attributed to the distinct functions of TNF-α on CD4+ T lymphocytes and cardiac microvascular endothelial cells, which play crucial roles in mediating autoimmune myocarditis at different stages. The conducted study highlights the significance of TNF-α expression in endothelial cells for leukocyte recruitment. The absence of TNF-α leads to impaired endothelial activation and reduced leukocyte adhesion, thereby preventing the transmigration of autoreactive T cells to the site of inflammation. Conversely, TNF-α plays a vital role in limiting the expansion of autoreactive T lymphocytes, thereby preventing the escalation of inflammation. The research also investigates how exosomes derived from CD4+ T cells are implicated in the regul ; ation of oxidative stress.. Experimental findings demonstrate that exosomes released by activated T cells induce oxidative stress in cardiac endothelial cells. The study reveals that the increase in NOX4 expression, driven by the transmission of ERK1/2 and MEK1/2 kinases, serves as the central mechanism responsible for the oxidative stress triggered by exosomes originating from T cells. Nevertheless, the exact roles of NOX4 within the heart and endothelium remain under scrutiny, as contradictory findings propose potential benefits and harms. In conclusion, this research underscores the need for further investigation to comprehend the intricate roles of TNF-α and its inhibitors in the treatment of heart disease. The study emphasizes the significant impact of TNF-α on autoreactive T lymphocytes and endothelial cells, as well as the involvement of T cell-derived exosomes and NOX4 in oxidative stress regulation. Future studies should explore potential therapeutic targets for TNF-α and NOX4 inhibition to enhance the treatment of myocarditis and related conditions.
Miejsce wydania:
Stopień studiów:
Instytucja nadająca tytuł:
Rada Dyscypliny Nauki medyczne
Promotor:
Data wydania:
Identyfikator:
Sygnatura:
Język:
Prawa dostępu:
Kolekcje, do których przypisany jest obiekt:
Data ostatniej modyfikacji:
28 paź 2024
Data dodania obiektu:
28 paź 2024
Liczba wyświetleń treści obiektu:
5
Liczba wyświetleń treści obiektu w formacie PDF
0
Wszystkie dostępne wersje tego obiektu:
http://dl.cm-uj.krakow.pl:8080/publication/5170
Wyświetl opis w formacie RDF:
Wyświetl opis w formacie OAI-PMH:
| Nazwa wydania | Data |
|---|---|
| ZB-140545 | 28 paź 2024 |
Obiekty
Podobne
Rolski, Filip
Jabłońska, Magdalena
Kleczyńska-Szpakiewicz, Weronika
Filip, Magdalena
Rubinkiewicz, Mateusz
Majcher, Paweł
Nazimek, Katarzyna
Urbański, Karol
