목차

List of Figures v
Part 1. Overexpression of Cathepsin S Induces Chronic Atopic Dermatitis in Mice
ABSTRACT 3
I. INTRODUCTION 4
II. MATERIALS AND METHODS 7
1. Plasmid construction 7
2. Generation and screening of transgenic mice 7
3. Reverse transcription-polymerase chain reaction (RT-PCR) analysis 8
4. Quantitative real-time PCR analysis 9
5. Behavioral experiments …..9
6. Antibodies …10
7. Histology and immunohistochemistry …10
8. Western blot analysis 11
9. Cytokine and IgE ELISA 11
10. Statistical analysis 12
III. RESULTS 13
1. CTSS induces PAR2 overexpression in CTSS-overexpressing mice
13
2. Atopic dermatitis symptoms in CTSS-overexpressing mice
16
3. Aggravation of inflammation and mast cell accumulation
18
4. Increased PAR2 expression caused by CTSS overexpression
21
5. Increased production of cytokines, chemokines, and IgE
25
IV. DISCUSSION 28
V. REFERENCES 33
Part 2. Over-expression of Cathepsin S in Mice Reduces Body Weight Gain and Modulates Adipocyte Differentiation
ABSTRACT 43
I. INTRODUCTION 45
II. MATERIALS AND METHODS 47
1. Plasmid construction 47
2. Generation of transgenic mice 47
3. Diet 48
4. Body weight, food intake and adipose tissue weight 49
5. Primary cell culture 49
6. Oil Red O staining 51
7. Quantitative real-time PCR analysis 51
8. Antibodies 52
9. Western blot analysis 52
10. Measurement of intracellular calcium by live cell microscopy 52
11. Cytokine ELISA 53
12. Statistical analyses 54
III. RESULTS 55
1. CTSS-overexpressing TG mice on a high-fat diet exhibit nonobese
phenotypes 55
2. Overexpression of CTSS prevents HFD-induced lipid accumulation in adipose tissue 60
3. Overexpression of CTSS delays pre-adipocyte differentiation 64
4. CTSS, endogenous agonist PAR2, and phosphorylated CAMKII
67
5. CTSS enhanced intracellular calcium concentration in
pre-adipocytes 70
6. CTSS induces pro-inflammatory cytokines to inhibit pre-adipocyte
differentiation 73
IV. DISCUSSION 75
V. REFERENCES 78
ABSTRACT (KOREAN) 83