The influence of CD206 in colonic macrophage to colorectal carcinogenesis
대장 마크로파지에서의 CD206이 대장암에 미치는 영향
- 주제(키워드) CD206(MRC1) , macrophage , AOM/DSS (azoxymethane/dextran sodium sulfate) , colorectal carcinogenesis , inflammation
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 장선영
- 발행년도 2024
- 학위수여년월 2024. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000033679
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
CD206 also known as MRC1, is C-type lectin receptor that expressed mainly on tissue macrophage and dendritic cell, plays an important role in immune homeostasis through endocytosis. It is well known as a marker of alternatively activated or immune regulatory macrophage. Usually, high level of CD206 expression is known to indicate poor prognosis in various solid cancers, but other cases that induce anti-cancer immunity have been reported, so its role is ambiguous. In particular, the role of CD206 or unique signaling in colorectal carcinogenesis have not been clarified. In this study, a colitis-associated colorectal cancer model was induced by AOM/DSS to confirm the difference in tumorigenesis between WT and CD206 deficient groups. Also, the effect and mechanism of CD206 on colorectal cancer were confirmed through immunological analysis. When colon macrophage subset of littermate control and CD206 deficient mice were analyzed in steady and inflammatory state, The CD11b+ CX3CR1high subset, which has immunoregulatory characteristic, significantly decreased in CD206 deficient mice. But, CD11b+ CX3CR1-/int subset, which has immunogenic characteristic, was increased. In AOM/DSS results, increased tumor nodules in colon were observed in the CD206 deficient group. In addition, inflammatory mediators secreted by tissues and macrophages increased more than WT group. It is expected that difference in colonic macrophage subsets due to deficiency of CD206 may affect the development of early colorectal carcinogenesis. Therefore, CD206 can act as protective role against to development of colitis-associated colorectal carcinogenesis. Keywords: CD206(MRC1), macrophage, AOM/DSS (azoxymethane/dextran sodium sulfate), colorectal carcinogenesis, inflammation
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 2
1. Bioinformatics analysis 2
2. Mice & Colitis and CAC model 2
3. Macrophage subset analysis 3
4. Foxp3+ Treg subset analysis 4
5. Culture for Bone marrow-derived macrophages 4
6. RNA extraction & Real-time PCR 5
7. Sorting for colon F4/80+ cells 6
8. Histology 6
9. Bacterial infection 7
10. Statistics 7
Ⅲ. RESULTS 11
A. Bioinformatics analysis of CD206 in colon adenocarcinoma. 11
B. Deficiency of CD206 increased inflammatory characteristic of macrophages in steady state. 14
C. Deficiency of CD206 can affect colon Treg population in steady state. 17
D. Deficiency of CD206 significantly affect colon inflammation in DSS state. 19
E. Deficiency of CD206 increased colonic tumor formation in AOM/DSS state. 23
F. Deficiency of CD206 in tissue induced inflammatory cytokines and tumor-related factors after AOM/DSS treatment. 26
G. Deficiency of CD206 in macrophage induced inflammatory cytokines and chemokine after AOM/DSS treatment. 28
H. Deficiency of CD206 showed higher defense against pathogenic bacterial infection. 30
Ⅳ. DISCUSSION 32
Ⅴ. CONCLUSION 35
REFERENCES 38
KOREAN ABSTRACT 40
