| نویسندگان | Farghadan M, Madreseh E, Akhtari M, Rokni M, Sadeghi Shaker M, Ahmadzadeh N, Akhlaghi M, Tahmasebi M, Sharafat Vaziri A, Jamshidi A, Farhadi E and Mahmoudi M |
|---|---|
| همایش | ICIA 2023 16th International Congress of Immunology |
| تاریخ برگزاری همایش | 27-29 April 2023 |
| محل برگزاری همایش | Tehran, Iran |
| نوع ارائه | سخنرانی |
| سطح همایش | بین المللی |
چکیده مقاله
Background: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) are the major pathological cells that display tumor-like behavior including aggressive phenotype, hyper-proliferation, and apoptosis resistance. The FLSs in RA patients are resistant to the endoplasmic reticulum (ER) stress-induced apoptosis. In this study, we evaluated the effect of APR246 (also named PRIMA-1MET) as a mutant p53 reactivator on ER stress genes related to apoptosis in RA-FLSs.
Methods: The FLSs samples were obtained from synovial tissues of RA patients (n=10). After characterization, the cells were treated with different doses of APR246. The rate of apoptosis and cell survival was measured by flow cytometry and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Furthermore, the mRNA levels of the selected ER stress genes involved in apoptosis including BIP, CHOP, GADD34, NOXA, HSPA1B, BCL2, and MCL1 were analyzed by Real-time PCR method in RA-FLSs.
Results: The results demonstrated that APR246 treatment in RA-FLSs leads to decreased cell survival, and induction of apoptosis in a dose-dependent manner. In addition, APR246 treatment significantly increased the mRNA expression of GADD34, CHOP, NOXA, and HSPA1B genes in RA-FLSs. Although APR246 treatment did not show any change in the mRNA expression levels of BIP, BCL2, and MCL1 genes in RA-FLSs.
Conclusion: Given the role of ER stress genes in RA-FLSs apoptosis, it seems that APR246 small molecule can be considered as a therapeutic approach in RA patients. However, further studies are needed to confirm these results.
Keywords: APR246, ER stress, Fibroblast-like synoviocytes (FLSs), Rheumatoid arthritis