Bruton's tyrosine kinase inhibition attenuates oxidative stress in systemic immune cells and renal compartment during sepsis-induced acute kidney injury in mice

Copyright © 2020 Elsevier B.V. All rights reserved..

Sepsis is a life-threatening condition which affects multiple organs including the kidney. Sepsis-induced acute kidney injury (AKI) is a major health burden throughout the globe. Pathogenesis of sepsis-induced AKI is complex; however, it involves both innate and adaptive immune cells such as B cells, T cells, dendritic cells (DCs), macrophages, and neutrophils. Bruton's tyrosine kinase (BTK) is reportedly involved in inflammatory and oxidative signaling in different immune cells, however its contribution with respect to sepsis-induced AKI has not been delineated. This study attempted to investigate the role of BTK and its inhibition on oxidizing enzymes NADPH oxidase (NOX-2) and inducible nitric oxide synthase (iNOS) in DCs, neutrophils, and B cells during AKI. Our data reveal that BTK is activated in DCs, neutrophils, and B cells which causes an increase in AKI associated biochemical markers such as serum creatinine/blood urea nitrogen, renal myeloperoxidase activity, and histopathological disturbances in renal tubular structures. Activation of BTK causes upregulation of NOX-2/iNOS/nitrotyrosine in these immune cells and kidney. Treatment with BTK inhibitor, Ibrutinib causes attenuation in AKI associated dysfunction in biochemical parameters (serum creatinine/blood urea nitrogen, renal myeloperoxidase activity) and oxidative stress in immune cells and kidney (iNOS/NOX2/lipid peroxides/nitrotyrosine/protein carbonyls). In summary, the current investigation reveals a compelling role of BTK signaling in sepsis-induced AKI which is evident from amelioration of AKI associated renal dysfunction after its inhibition.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:90

Enthalten in:

International immunopharmacology - 90(2021) vom: 01. Jan., Seite 107123

Sprache:

Englisch

Beteiligte Personen:

Nadeem, Ahmed [VerfasserIn]
Ahmad, Sheikh F [VerfasserIn]
Al-Harbi, Naif O [VerfasserIn]
Ibrahim, Khalid E [VerfasserIn]
Alqahtani, Faleh [VerfasserIn]
Alanazi, Wael A [VerfasserIn]
Mahmood, Hafiz M [VerfasserIn]
Alsanea, Sary [VerfasserIn]
Attia, Sabry M [VerfasserIn]

Links:

Volltext

Themen:

1X70OSD4VX
Acute kidney injury
Adenine
Agammaglobulinaemia Tyrosine Kinase
B cells
Btk protein, mouse
Cybb protein, mouse
Dendritic cells
EC 1.14.13.39
EC 1.6.3.-
EC 2.7.10.2
Enzyme Inhibitors
INOS
Ibrutinib
JAC85A2161
Journal Article
NADPH Oxidase 2
NOX2
Neutrophils
Nitric Oxide Synthase Type II
Nos2 protein, mouse
Piperidines

Anmerkungen:

Date Completed 25.05.2021

Date Revised 26.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2020.107123

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM31736149X