BTK inhibitor ibrutinib reduces LPS-induced inflammation in C8-B4 microglia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F25%3A10505543" target="_blank" >RIV/00064165:_____/25:10505543 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10505543 RIV/00216208:11310/25:10505543

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Z0kDLd2iOi" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Z0kDLd2iOi</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.17179/excli2025-8695" target="_blank" >10.17179/excli2025-8695</a>

Jazyk výsledku

angličtina

Název v původním jazyce

BTK inhibitor ibrutinib reduces LPS-induced inflammation in C8-B4 microglia

Popis výsledku v původním jazyce

In this study, we examined the potential of Bruton tyrosine kinase (BTK) inhibitor ibrutinib to mitigate neuroinflammation in C8-B4 microglial cells activated by the bacterial endotoxin lipopolysaccharide (LPS). Our objective was to enhance understanding of its mechanism of action, particularly in relation to its anti-inflammatory, and antioxidant potential of ibrutinib. Here, mouse microglial C8-B4 cells were treated with ibrutinib (1 and 10 μM) or vehicle (1 % DMSO) for 1 h, followed by lipopolysaccharide (LPS 1 μg/mL) for 23 h. We observed that ibrutinib significantly decreased LPS-induced nitric oxide levels and nitric oxide synthase 3 (NOS3) expression. In parallel, ibrutinib decreased cell senescence induced by LPS in microglia. Ibrutinib notably diminished the elevation of tumor necrosis factor-α (TNF-α), triggered by LPS in C8-B4 microglia. It also modulated Toll-like receptor 4 (TLR4) expression induced by LPS. Moreover, ibrutinib markedly lowered the augmented levels of nuclear factor kappa beta (NF-kβ) and phosphorylated NF-kβ (pNF-kβ) induced by LPS, indicating its capacity to mitigate LPS-induced neuroinflammatory reactions by hindering TLR4/NF-kβ pathway. Additionally, these beneficial effects are associated with regulation of the Nrf2/HO-1 pathway. The present results suggest that treatment with ibrutinib may contribute to the preservation of mitochondrial function, as evidenced by its ability to reduce reactive oxygen species (ROS) production. While these findings provide important insights into the potential neuroprotective mechanisms of ibrutinib, the precise molecular pathways involved in mitochondrial preservation require further investigation. Collectively, these data support the therapeutic potential of ibrutinib in mitigating neuroinflammation-related mitochondrial dysfunction and highlight its promise as a candidate for treating neurodegenerative disorders characterized by oxidative stress and impaired mitochondrial integrity.

Název v anglickém jazyce

BTK inhibitor ibrutinib reduces LPS-induced inflammation in C8-B4 microglia

Popis výsledku anglicky

In this study, we examined the potential of Bruton tyrosine kinase (BTK) inhibitor ibrutinib to mitigate neuroinflammation in C8-B4 microglial cells activated by the bacterial endotoxin lipopolysaccharide (LPS). Our objective was to enhance understanding of its mechanism of action, particularly in relation to its anti-inflammatory, and antioxidant potential of ibrutinib. Here, mouse microglial C8-B4 cells were treated with ibrutinib (1 and 10 μM) or vehicle (1 % DMSO) for 1 h, followed by lipopolysaccharide (LPS 1 μg/mL) for 23 h. We observed that ibrutinib significantly decreased LPS-induced nitric oxide levels and nitric oxide synthase 3 (NOS3) expression. In parallel, ibrutinib decreased cell senescence induced by LPS in microglia. Ibrutinib notably diminished the elevation of tumor necrosis factor-α (TNF-α), triggered by LPS in C8-B4 microglia. It also modulated Toll-like receptor 4 (TLR4) expression induced by LPS. Moreover, ibrutinib markedly lowered the augmented levels of nuclear factor kappa beta (NF-kβ) and phosphorylated NF-kβ (pNF-kβ) induced by LPS, indicating its capacity to mitigate LPS-induced neuroinflammatory reactions by hindering TLR4/NF-kβ pathway. Additionally, these beneficial effects are associated with regulation of the Nrf2/HO-1 pathway. The present results suggest that treatment with ibrutinib may contribute to the preservation of mitochondrial function, as evidenced by its ability to reduce reactive oxygen species (ROS) production. While these findings provide important insights into the potential neuroprotective mechanisms of ibrutinib, the precise molecular pathways involved in mitochondrial preservation require further investigation. Collectively, these data support the therapeutic potential of ibrutinib in mitigating neuroinflammation-related mitochondrial dysfunction and highlight its promise as a candidate for treating neurodegenerative disorders characterized by oxidative stress and impaired mitochondrial integrity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

EXCLI Journal

ISSN

1611-2156

e-ISSN

1611-2156

Svazek periodika

24

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

18

Strana od-do

1482-1499

Kód UT WoS článku

001609873500001

EID výsledku v databázi Scopus

2-s2.0-105024998554