The role of aryl hydrocarbon receptor in colon macrophages to repress colorectal carcinogenesis
- 주제(키워드) Colorectal cancer , Aryl hydrocarbon receptor , Macrophages , Colon , Inflammation
- 주제(DDC) 615.1
- 발행기관 아주대학교
- 지도교수 장선영
- 발행년도 2022
- 학위수여년월 2022. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000031445
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Colorectal cancer is related to inflammatory bowel disease which is a chronic inflammatory state in the gastrointestinal tract. Gut macrophage expressing CX3CR1 plays an immunoregulatory role in the gut immune homeostasis. Aryl hydrocarbon receptor (AhR), a ligand-dependent endogenous receptor plays a role as a transcription factor to xenobiotic element which is considered as an environmental sensor. Although the roles of AhR in several immune cells such as T cells have been extensively exploited, their role in gut macrophages needs to be investigated. The objective of the study is to investigate the role of AhR in colon macrophages and furthermore in colorectal cancer. AhR deficiency on CX3CR1+ macrophages induces more infiltration of pro-inflammatory type macrophage into inflamed colon tissue. AhR deficient macrophage secreted enhanced chemokines such as CCL2, CCL7, CCL8, and CCL12 which are associated with monocyte infiltration. Interestingly, AhR deficient macrophages produced high level of IL-6 which is associated with tumor progression. Mice having AhR deficient macrophages increased the number of tumor nodules in AOM/DSS model. These results suggested that AhR in colon macrophages suppresses colorectal tumor promotion via conditioning an immune-regulatory gut environment.
more목차
I. INTRODUCTION 1
II. MATERIALS AND METHODS 3
1. Mice 3
2. Colon macrophage isolation 3
3. Magnisort and RNA extraction 4
4. Real-time PCR 4
5. Flow cytometry 5
6. Experimental procedure and histological strategy 5
7. Statics 6
III. RESULTS 10
A. AhR deficiency of CX3CR1+ cells does not affect immunological inflammatory status at AOM/DSS state 10
B. AhR deficiency of CX3CR1+ cells induces more colonic tumor formation in vivo 12
C. AhR deficiency of CX3CR1 cells affects colonic macrophage polarization at steady-state 15
D. AhR deficiency of CX3CR1 cells induces more severe inflammatory condition at DSS induced colitis state 17
E. AhR deficiency of CX3CR1+ cells attracts more pro-inflammatory monocytes and macrophages at AOM/DSS state 19
F. AhR deficiency in CX3CR1+ macrophages induces more production of chemokine and tumor promotive cytokine at DSS colitis state 21
IV. DISCUSSION 25
V. CONCLUSION 27
REFERENCES 28
KOREAN ABSTRACT 30
