PhD Scientific Days 2025

Poster Session I. - F: Pharmaceutical Sciences and Health Technologies

A New Therapeutic Approach in Heart Failure: A Cell-Based Platform for Testing Inflammasome Inhibitors

Előadó neve

Dr. Jezsoviczky Sára

Neptun code

EFTL91

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36703182551

Előadó e-mail címe

jezsoviczky.sara@semmelweis.hu

Az előadás címe

A New Therapeutic Approach in Heart Failure: A Cell-Based Platform for Testing Inflammasome Inhibitors

Szerző(k) neve és munkahelye

Jezsoviczky Sára^1,2, Kovács Andrea^1,2,3, Kocsis Márton^1,2,3, Kozma Gergely⁴, Szabó Márta^1,2, Ferdinandy Péter^1,2,5,6, Varga Zoltán V.^1,2,3,7, Onódi Zsófia^1,2,3,7

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1085 Budapest, Hungary
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, H-1085 Budapest, Hungary
3: HCEMM-SU Cardiometabolic Immunology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary
4: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary
5: Pharmahungary Group, H-6722 Szeged, Hungary.
6: HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary
7: MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Semmelweis University, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session I. - F: Pharmaceutical Sciences and Health Technologies

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Inflammasome activity is a key contributor in chronic inflammatory conditions, such as heart failure, so modulators of the NLRP3 inflammasome could be utilized in its therapy. The activation is a two-step process: priming, which upregulates the expression of inflammasome components, then activation, resulting in oligomerization of proteins and cytokine secretion (e.g., IL-1β). Discovering compounds that inhibit NLRP3 could lead to new methods to treat heart failure.
Aims: To develop a cell-based platform using a human monocytic cell line to evaluate potential inflammasome inhibitors.
Methods: THP1-ASC-GFP reporter cells were used to model inflammasome activation. NLRP3 inflammasome induction involved priming cells with lipopolysaccharide (LPS) for 24 hours, followed by activation with nigericin. Drug candidates — probenecid, sotagliflozin, canagliflozin, and linagliptin — were tested alongside known inhibitors MCC950 (NLRP3 inhibitor) and VX-765 (caspase-1 inhibitor). Cell viability was assessed to determine cell survival. Imaging flow cytometry was used to monitor inflammasome priming and activation, while Western blotting and caspase-1 activity assay were used to evaluate downstream signaling.
Results: Treatment with LPS and nigericin induced NLRP3 inflammasome activation, as demonstrated by increased ASC diffuse+ (18.34% to 55.67%) and ASC speck+ cell populations (0.97% to 49.40%), IL-1β cleavage and caspase-1 activity, accompanied by reduced cell viability. MCC950 suppressed NLRP3 activation (49.40% to 21.08%) and inhibited maturation of inflammatory mediators. In contrast, VX-765 had no effect on NLRP3 activation but reduced IL-1β cleavage (1.0 to 0.11) and caspase-1 activity. Among the tested compounds, canagliflozin and linagliptin significantly decreased cleaved IL-1β levels (to 0.45 and 0.53, respectively).
Conclusions: Our screening platform offers a tool to examine inflammasome activation and inhibition in THP1-ASC-GFP cells, supporting the discovery of new anti-inflammatory drugs. Our data suggests that approved drugs possess inflammasome modulatory effects, calling for further research into their mechanism of action.
Funding: The work was supported by János Bolyai Research Scholarship. Project no. RRF-2.3.1-21-2022-00003 has been implemented with the support provided by the European Union.

University

Semmelweis University

Supervisor

Dr. Gulyás-Onódi Zsófia

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9021

Start

17:18

End

17:24