아주대학교

목차

Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS and METHODS 5
2.1. Materials 5
2.2. Animals 5
2.3. Generation of Cnr1 mutant mice and genotyping 5
2.4. Human samples 6
2.5. Cell lines and primary cell cultures 6
2.6. Rimonabant synthesis and characterization 7
2.7. Compound 1 8
2.8. Compound 2 8
2.9. Compound 3 9
2.10. Compound 4 9
2.11. Compound 5 10
2.12. Generation of CB1R-FAM 10
2.13. Western blotting analysis 11
2.14. Cell isolation from skin 11
2.15. RNA immunoprecipitation 12
2.16. IMQ- and rIL-23-induced psoriasis models 12
2.17. Histology, immunostaining, immunohistochemistry and image processing/analysis 13
2.18. In vivo macrophage depletion 14
2.19. Plasmids, siRNA, and transfection 14
2.20. Adenovirus infection 15
2.21. Flow cytometry 15
2.22. RNA extraction and RT-qPCR 16
2.23. RNA sequencing and bioinformatics analysis 16
2.24. KEGG pathway analysis 17
2.25. Weighted gene co-expression network analysis (WGCNA) and Protein-protein interaction (PPI) network analysis 17
2.26. Biotin pull down assay 18
2.27. In vivo skin penetration assay 18
2.28. In vitro macrophage polarization 18
2.29. ELISA 19
2.30. QUANTIFICATION AND STATISTICAL ANALYSIS 19
Ⅲ. RESULTS 26
3.1. CB1R expression is elevated in psoriatic skin and enriched in infiltrating macrophages 26
3.2. Pharmacological CB1R blockade ameliorates IMQ-induced psoriasis-like dermatitis and restores epidermal barrier function 38
3.3. Macrophages are required for the anti-psoriatic effect of RIMO 53
3.4. Myeloid cell–specific CB1R deficiency mitigates psoriasis-like phenotypes through suppression of M1 macrophages 57
3.5. Immune cell transcriptomics reveal reversal of disease programs by CB1R blockade and nominate an AUF1–NLRP3 axis 71
3.6. AUF1 represses Nlrp3 mRNA via 3′ UTR binding to attenuate psoriasis-like phenotypes in vivo 84
3.7. CB1R regulates psoriatic skin inflammation through the AUF1–NLRP3 axis in vivo 91
Ⅳ. DISCUSSION 97
Ⅴ. CONCLUSION 99
Ⅵ. REFERENCE 100
Ⅶ. ABSTRACT IN KOREAN (국문초록) 109