PhD Scientific Days 2023

Molecular Sciences IV.

The effect of a specific Syk tyrosine-kinase inhibitor in autoantibody-induced experimental arthritis

Előadó neve

Káposztás, Eszter

Neptun code

B8B0QC

Előadó munkahelye

Department of Physiology

Előadó telefonszáma

06302312287

Előadó e-mail címe

kaposztas.eszter@med.semmelweis-univ.hu

Az előadás címe

The effect of a specific Syk tyrosine-kinase inhibitor in autoantibody-induced experimental arthritis

Szerző(k) neve és munkahelye

Eszter Káposztás1,2, Attila Mócsai1 and Tamás Németh1,2,3

1 Department of Physiology, Semmelweis University, Budapest, Hungary
2 MTA-SE “Lendület” Translational Rheumatology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
3 Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences IV.

Language of the presentation

Hungarian

Preferred session

Health Sciences

Összefoglaló szövege

Introduction: The Syk tyrosine-kinase is an important component of immune (e.g. Fc) receptor signalling. It was previously shown that the absence of Syk from the hematopoietic compartment resulted in a total protection in autoantibody-induced experimental arthritis. These data with additional observations raised the possibility that Syk could be a potential therapeutic target in human autoimmune arthritis.
Aims: Here, we tested the effect of the inhibition of the Syk tyrosine-kinase in autoantibody-induced experimental arthritis by entospletinib, a second generation, Syk-selective inhibitor, which has a tolerable safety profile (according to hematological clinical trials).
Methods: Experimental arthritis was induced by an intraperitoneal injection of K/BxN serum. Entospletinib or vehicle was administered orally twice a day. Arthritis was followed by clinical scoring and ankle thickness measurement. Myeloid cell recruitment to the joints and the proliferation and activation status of synovial fibroblasts (FLS) was detected by flow cytometry. The synovial cytokine levels were measured by ELISA. The immune complex-stimulated superoxide production of neutrophils and macrophages was detected by a cytochrome c-reduction or a luminometric assay, while the cell spreading was followed by phase contrast microscopy.
Results: The oral administration of entospletinib decreased the severity of experimental arthritis. In line with this, the myeloid cell accumulation and the synovial cytokine levels were lower in the entospletinib-treated group. However, the presence of the inhibitor did not significantly reduce the proliferation and the activation status of FLS. In contrast to this, entospletinib dose-dependently decreased the superoxide release of the immune complex-triggered neutrophils and macrophages, and also the cell spreading of neutrophils.
Conlcusion: The Syk-selective, second generation inhibitor entospletinib effectively reduced the inflammation in autoimmune arthritis in mice, which raises the possibility that entospletinib could be a drug candidate in the treatment of human autoimmune joint inflammation in the future.
Funding: This work was funded by the Hungarian National Research, Development and Innovation Office and the Lendület program of the Hungarian Academy of Sciences. E.K. is a recipient of a Semmelweis University 250+ Scholarship.

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Dr. Tamás Németh

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7430

Start

16:00

End

16:15

Authors (legacy)

Eszter Káposztás1,2, Attila Mócsai1 and Tamás Németh1,2,3

1 Department of Physiology, Semmelweis University, Budapest, Hungary
2 MTA-SE “Lendület” Translational Rheumatology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
3 Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest, Hungary