Borik Asit LPS ile Uyarılan Glioblastoma Hücrelerinde İnflamazom Aktivasyonunu İnhibe Eder

Year 2024, , 224 - 231, 22.05.2024

Ceyhan Hacıoğlu

https://doi.org/10.33631/sabd.1408373

Abstract

Amaç: En sık görülen primer beyin tümörleri olan gliomalar, çeşitli klinik özellikler ve kötü prognoz sergiler. İnflamazom aktivasyonu, glioma gelişiminde rol oynayan, nükleotid bağlama alanı lösin açısından zengin aile pirin içeren 3 (NLRP3) gibi inflamazomlar tarafından düzenlenen, merkezi sinir sistemindeki inflamatuar mikro ortamla yakından bağlantılıdır. Ancak NLRP3'ün insan gliomasındaki rolü belirsizliğini koruyor. Bu çalışma borik asidin U87 glioblastoma hücreleri ve NLRP3 inflamazom aktivasyonu üzerindeki etkilerini araştırmaktadır.
Gereç ve Yöntemler: Enzime bağlı immünosorbent analizi (ELISA) yöntemini kullanarak 24, 48 ve 72 saat boyunca çeşitli borik asit konsantrasyonlarına maruz kalan U87 hücrelerindeki hücre canlılığını, 5-bromo-2'-deoksiüridin (BrdU), NLRP3, interlökin (IL)-1β, IL-18, kaspaz 1, apoptoz indükleyici faktörü (AIF) ve sitokrom c seviyelerini değerlendirdik.
Bulgular: Sonuçlarımız, 0-6,4 mM aralığında borik asit konsantrasyonlarına maruz kalmanın ardından U87 hücre canlılığında zamana ve konsantrasyona bağlı bir azalma olduğunu ortaya koydu. BrdU analizi, 24 saatlik borik asit uygulamasından sonra hücre çoğalmasının azaldığını gösterdi. Lipopolisakkarit (LPS) kullanılarak U87 hücrelerinde inflamatuar aktivasyonun uyarılması, yüksek NLRP3, IL-1β, IL-18 ve kaspaz-1 seviyeleriyle sonuçlandı. Ancak borik asit uygulaması bu etkiyi ortadan kaldırarak inflamazom aktivasyonu azalttı. Ayrıca borik asit+LPS tedavisi AIF ve sitokrom c düzeylerini indükleyerek apoptoza yol açtı.
Sonuç: Bulgularımız borik asidin U87 hücrelerinde NLRP3 inflamatuar aktivasyonunu inhibe ettiğini, dolayısıyla hücre canlılığını baskıladığını gösterdi. Bu, borik asidin NLRP3 inflamatuarını engelleyerek inflamatuar mikro ortamı hafiflettiğini ve glioblastomanın ilerlemesinde potansiyel terapötik avantajlar sunduğunu göstermektedir.

Keywords

İnflamazom aktivasyonu, Glioblastoma, Borik asit

BBoric Acid Inhibits Inflammasome Activation in LPS-Stimulated Glioblastoma Cells

Abstract

Aim: Gliomas, the most common primary brain tumors, exhibit diverse clinical features and a poor prognosis. Inflammasome activation is closely linked to the inflammatory microenvironment in the central nervous system, regulated by inflammasomes like nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3), implicated in glioma development. However, NLRP3's role in human glioma remains unclear. This study explores the effects of boric acid on U87 glioblastoma cells and NLRP3 inflammasome activation.
Material and Methods: Employing the enzyme-linked immunosorbent assay (ELISA) method, we assessed cell viability, 5-bromo-2'-deoxyuridine (BrdU), NLRP3, interleukin (IL)-1β, IL-18, caspase 1, apoptosis inducing factor (AIF), and cytochrome c levels in U87 cells exposed to various concentrations of boric acid for 24, 48, and 72 hours.
Results: Our findings revealed a time- and concentration-dependent reduction in U87 cell viability following exposure to boric acid concentrations within the 0-6.4 mM range. BrdU analysis indicated decreased cell proliferation after 24 hours of boric acid application. Stimulation of inflammasome activation in U87 cells using lipopolysaccharide (LPS) resulted in elevated levels of NLRP3, IL-1β, IL-18, and caspase-1. However, boric acid application countered this effect, reducing inflammasome activation. Additionally, treatment with boric acid+LPS induced AIF and cytochrome c levels, leading to apoptosis.
Conclusion: Our results demonstrated that boric acid inhibited NLRP3 inflammasome activation in U87 cells, consequently suppressing cell viability. This suggests that by impeding the NLRP3 inflammasome, boric acid mitigates the inflammotary
microenvironment, offering potential therapeutic advantages in the progression of glioblastoma.

Keywords

Inflammasome activation, Glioblastoma, Boric acid

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