Document Type : Original Article(s)
Authors
- Afrouz Asgarian 1
- Zahra Hesari 2
- Mehrdad Aghaei 3
- Zahra Faghhian 2
- Romina Malakouti 4
- Sima Besharat 5
- Koushan Sineh Sepehr 4
1 Clinical Research Development Unit, Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran
2 Metabolic Disorders Research Center, Biomedical Research Institute, Golestan University of Medical Sciences, Gorgan, Iran
3 Golestan Rheumatology Research Center, Biomedical Research Institute, Golestan University of Medical Science, Gorgan, Iran
4 Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
5 Golestan Research Center of Gastroenterology and Hepatology, Jorjani Clinical Sciences Research Institute, Golestan University of Medical Sciences, Gorgan, Iran
Abstract
Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial joints. In response to inflammation, sirtuin-1 (SIRT-1) plays a regulatory role by modulating inflammatory signaling pathways and protecting against further tissue damage. Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine released predominantly by pyroptotic immune cells. Visfatin, an adipokine secreted by lymphocytes and other immune cells, is increasingly recognized as a pro-inflammatory mediator implicated in various rheumatologic disorders. This study aimed to evaluate the expression levels of SIRT-1, IL-18, and visfatin genes in immune cells of AS patients.
Methods: In 2022, this cross-sectional study was conducted in Gorgan, Iran. Peripheral blood mononuclear cells (PBMCs) were isolated from a total of 49 AS patients, including patients undergoing treatment with three doses of etanercept and the newly diagnosed, treatment-naïve patients. Total RNA was extracted from PBMCs, and complementary DNA (cDNA) was synthesized. Gene expression levels of SIRT-1, IL-18, and visfatin were quantified using real-time PCR, and data were analyzed using SPSS v16 and GraphPad Prism 9 with Student’s t test. A significant difference was considered as P<0.05.
Results: SIRT-1 expression was significantly lower in newly diagnosed AS patients than in the etanercept-treated group (P=0.041). Visfatin expression was significantly higher in the new case group than in the treated group (P=0.021). Similarly, IL-18 expression was significantly higher in new cases than in etanercept-treated patients (P=0.028).
Conclusion: Etanercept significantly upregulates SIRT-1 expression while suppressing IL-18 and visfatin levels in AS patients, highlighting its pleiotropic anti-inflammatory mechanisms beyond TNF-α blockade. These findings provide novel insights into the molecular pathways modulated by anti-TNF therapy, particularly the interplay between SIRT1-mediated epigenetic regulation and adipokine-driven inflammation.
Highlights
Afrouz Asgarian (Google Scholar)
Koushan Sineh Sepehr (Google Scholar)
Keywords
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