PhD Scientific Days 2024

Poster Session E - Molecular Medicine 2.

The effect of selective Syk inhibition on autoantibody-induced experimental arthritis

Előadó neve

Ms. Káposztás, Eszter

Neptun code

B8B0QC

Előadó munkahelye

Semmelweis University, Department of Physiology

Előadó telefonszáma

06302312287

Előadó e-mail címe

kaposztas.eszter@semmelweis.hu

Az előadás címe

The effect of selective Syk inhibition on autoantibody-induced experimental arthritis

Szerző(k) neve és munkahelye

Eszter Káposztás¹, Attila Mócsai¹, Tamás Németh¹

1: Semmelweis University, Department of Physiology

Bemutatás módja

Poszter

Szekció

Poster Session E - Molecular Medicine 2.

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction: Syk is a non-receptor tyrosine-kinase which is an important component of immune (e.g. Fc) receptor signalling. It has been shown that the absence of Syk from the hematopoietic compartment resulted in a total protection in autoantibody-induced experimental arthritis. The above mentioned results with additional observations raised the possibility that Syk could be a potential therapeutic target in human autoimmune arthritis.
Aim: In our experiments, we tested the effect of entospletinib a second generation, highly Syk-selective inhibitor in the Fcγ-receptor and integrin-ligand mediated autoantibody-induced experimental arthritis.
Methods: Experimental arthritis was induced by a single intraperitoneal injection of K/BxN serum. Entospletinib or vehicle was administered orally twice a day. The severity of arthritis was followed by visible clinical scoring and ankle thickness measurement. Myeloid cell recruitment to the joints was detected by flow cytometry. The levels of inflammatory mediators in the supernatants of affected joint samples or of in vitro stimulated neutrophils were measured by ELISA. The immune complex- and integin-ligand-activated superoxide production of neutrophils was detected by a cytochrome c-reduction assay, while 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 number of synovial neutrophils and synovial cytokine levels were decreased in the entospletinib-treated group. Meanwhile, entospletinib dose-dependently decreased the immune complex-stimulated and integrin-mediated neutrophil cell responses, like superoxide release, cell spreading and cytokine production.
Conclusion: 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. Eszter Káposztás is a recipient of a Semmelweis University 250+ Scholarship.

University

Semmelweis University

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

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7430

Start

15:20

End

15:23