S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
The role of α-enolase on the production of interleukin-32 in concanavalin A mediated inflammation and rheumatoid arthritis
Concanavalin A 염증 매개 모델과 류마티스 관절염에서 인터루킨-32 생성과 관련한 알파 에놀레이즈의 역할에 관한 연구
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 2. 강재승.
- Interleukin (IL)-32 is produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. It has recently been reported that it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6 and IL-8 and its expression is highly increased in the rheumatoid arthritis (RA) patients. α-Enolase (ENO1) is a glycolytic enzyme and the stimulation of ENO1 induces high level of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and macrophages from RA patients. In addition, there are many reports that anti-ENO1 antibody is correlated with the disease progression of RA. It implies that ENO1 could regulate IL-32 production during inflammation related with the pathogenesis of RA. Therefore, I performed whether ENO1 is involved in the production of IL-32 underinflammatory condition using Con A-activated PBMCs and RA PBMCs. As a result, it was confirmed by RT-PCR and ELISA that the expression of IL-32 at mRNA and protein levels was increased by stimulation with anti-ENO1 mAb. To investigate the signaling pathway that is stimulated with anti-ENO1 mAb, I did immunoblotting for nuclear factor (NF)-κB and p38 mitogen activated protein kinase (MAPK) pathway. Phosphorylated p65 and p38 MAPK were increased by ENO1 stimulation. Finally, I confirmed that the increased IL-32 production by ENO1 stimulation was inhibited by the pre-treatment of BAY11-7082, SB203580. Taken together, these results suggest that ENO1 plays an important role in inflammation through the induction of IL-32 production that is mediated with the activation of NF-κB and p38 MAPK pathway.