Immunomodulatory Effects of a Selective STAT3 Inhibitor in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus
- 주제(키워드) Systemic lupus erythematosus , STAT3 , Inhibitor , HCB-5300 , Peripheral blood mononuclear cells , Cytokines
- 주제(DDC) 547
- 발행기관 아주대학교 일반대학원
- 지도교수 서창희
- 발행년도 2026
- 학위수여년월 2026. 8
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000036181
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Aberrant overactivation of signal transducer and activator of transcription 3 （STAT3） is implicated in the development and progression of systemic lupus erythematosus （SLE） by inducing the overproduction of inflammatory cytokines and contributing to immunological dysregulation. In this study, we investigated whether HCB-5300, a selective STAT3 allosteric inhibitor, could ameliorate the imbalance induced by the overexpression of inflammatory cytokines and the breakdown of immune tolerance in peripheral blood mononuclear cells （PBMCs） of patients with SLE. HCB-5300 selectively inhibited STAT3 phosphorylation in PBMCs from patients with SLE. Notably, it induced an increase in the expression of the anti- inflammatory cytokine IL-10, alongside a concomitant decrease in the mRNA expression of pro-inflammatory cytokines including IL-6, TNFα, and IL-17A. These findings demonstrate that selective STAT3 inhibition effectively polarizes the inflammatory immune microenvironment in SLE PBMCs toward an anti- inflammatory phenotype. Consequently, the selective inhibitor HCB-5300 holds great potential as a promising targeted therapeutic strategy for SLE.
more목차
1. Introduction 1
2. Materials and Methods 4
2.1 Study participants 4
2.2 Ethics approval and consent to participate 6
2.3 PBMC isolation 6
2.4 CCK-8 cell viability assay 6
2.5 Treatment of PBMCs 7
2.6 Real-time quantitative PCR 7
2.7 Western blotting 8
2.8 Enzyme-Linked Immunosorbent Assay（ELISA） 9
2.9 Statistical analysis 10
3. Results 11
3.1 Effect of HCB-5300 on PBMC viability 11
3.2 HCB-5300 shifts cytokine gene expression toward a less inflammatory profile in SLE PBMCs 12
3.3 HCB-5300 selectively suppresses STAT3 phosphorylation in SLE PBMCs 14
3.4 HCB-5300 enhances IL-10 secretion and shows non-significant decreasing trends in pro-inflammatory cytokines in SLE PBMCs 16
4. Discussion 18
5. Conclusion 24
6. References 25
7. 국문 초록 30
