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MRC1 Maintains Immunoregulatory Macrophages and Suppresses Colorectal Tumor Development

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Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 4
A. Mice 4
B. AOM/DSS-induced colorectal cancer model 4
C. DSS-induced colitis model 4
D. Cell isolation from colon lamina propria 5
E. Cell isolation from tissue 6
F. Flow cytometry 6
G. Bone marrow-derived macrophage 6
H. Magnetic sorting of F4/80+ cells 7
I. RNA extraction and Real-time PCR 7
J. IL-10 ELISA 8
K. Histology 8
L. Statistics 9
Ⅲ. RESULTS 11
A. Validation of the wild-type (WT) and Mrc1 knockout (KO) mouse system. 11
B. MRC1 protects against AOM/DSS-induced colitis and colorectal cancer and attenuates colonic pathology. 13
C. MRC1 suppresses the formation of colorectal tumor in the AOM/DSS model. 15
D. Absence of MRC1 promotes inflammation and increases disease severity in the DSS-induced colitis model. 19
E. Comparison of regulatory T cell (Treg) populations between WT and Mrc1 KO mice following DSS treatment. 22
F. Absence of MRC1 affects the macrophage subtype polarization under various conditions. 24
G. Comparison of gene expression of BMDMs between WT and Mrc1 KO mice after the treatment of LPS or IL-4. 28
H. Comparison of gene expression in colonic macrophages between WT and Mrc1 KO mice after AOM/DSS treatment. 31
I. Comparison of gene expression in colonic macrophages between WT and Mrc1 KO mice after DSS treatment. 33
J. Absence of MRC1 increases IL-10 protein levels in various states. 35
Ⅳ. DISCUSSION 37
Ⅴ. CONCLUSION 39
REFERENCES 41
KOREAN ABSTRACT 43

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