The role of CCR1 expression in herpes simplex virus-induced Behçet's disease mouse model : The role of CCR1 expression in herpes simplex virus-induced Behçet's disease mouse model
단순 포진 바이러스 1형에 의해 유도된 베체트병 마우스 모델에서 CCR1 발현의 역할
- 주제(키워드) Behçet's disease , CCL3 , CCR1 , herpes simplex virus , inflammation , mouse model
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 Seonghyang Sohn
- 발행년도 2024
- 학위수여년월 2024. 2
- 학위명 박사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000033783
- 본문언어 한국어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
The role of CCR1 expression in herpes simplex virus- induced Behçet's disease mouse model Behçet's disease (BD) is a chronic systemic inflammatory disease with unclear etiopathogenesis. C-C chemokine receptor type 1 (CCR1) ligand, C-C motif ligand 3 (CCL3) has been identified as down-regulation expression in peripheral blood leukocytes (PBL) and lymph nodes (LN), even though the protein expression of CCR1 in BD remains unclear. The objective of this study was to analyze the role of CCR1 and its ligand CCL3 in a herpes simplex virus-induced mouse model of BD. The frequencies of CCR1+ cells on the surface and in the cytoplasm of PBL and LN were analyzed by flow cytometry. The CCR1+ cells were significantly down-regulated in BD mice compared with the normal control and symptom-free control mice. Colchicine and pentoxifylline treatment improved the symptoms of BD and increased the frequencies of CCR1+ cells in BD mice. Treatment with chemokine CCL3, a ligand of CCR1, caused BD symptoms to deteriorate in 10 of 16 BD mice (62.5%) via down-regulation of CCR1+ cells. Anti-CCL3 antibody treatment ameliorated BD symptoms in 10 of 20 mice (50%) and significantly decreased the disease severity score compared with CCL3-treated BD mice (P = 0.01) via up-regulation of CCR1+ cell frequencies. In patients with BD, plasma levels of CCL3 in an active state were significantly higher than in healthy control individuals (P = 0.02). These results show that the up-regulation of CCR1+ cells was related to the control of systemic inflammation of BD in mouse models. Keywords: Behçet's disease; CCL3; CCR1; herpes simplex virus; inflammation; mouse model.
more목차
1. INTRODUCTION 1
2. MATERIALS AND METHODS 3
2.1. Animal experiments 3
2.2. Symptoms of Behçet's disease in mice 3
2.3. Flow cytometry 4
2.4. Western blot analysis 4
2.5. Administration of cytokines, ligand, and antagonist 5
2.6. Drug treatments 6
2.7. Patients with Behçet's disease 6
2.8. CCL3 ELISA 7
2.9. Statistical analysis 8
3. RESULTS 9
3.1. Frequencies of CCR1+ cells in Behçet's disease mice 9
3.2. Interleukin-10 and GM-CSF affect frequencies of CCR1+ cells in normal mice 14
3.3. Interleukin-10 and GM-CSF up-regulate frequencies of CCR1+ cells in Behçet's disease mice 18
3.4. CCL3 down-regulates the expression of CCR1+ cells in normal mice 23
3.5. BX471, a CCR1 antagonist, does not down-regulate CCR1+ cells in normal mice 27
3.6. CCL3 and BX-471 regulates the expression of CCR1+ cells and deteriorates symptoms in Behçet's disease mice 30
3.7. Drug treatment regulates frequencies of CCR1+ cells in normal mice 34
3.8. Drug treatment regulates frequencies of CCR1+ cells in Behçet's disease mice 38
3.9. Anti-CCL3 antibody up-regulates the expression of CCR1+ cells normal mice 43
3.10. Anti-CCL3 antibody up-regulates the expression of CCR1+ cells and improves symptoms in Behçet's disease mice 47
3.11. Behcet's disease patient clinical and therapeutic history 53
3.12. Plasma levels of CCL3 in patients with Behçet's disease 56
4. DISCUSSION 58
5. CONCLUSION 63
