Title Page
Contents
ABBREVIATION 9
ABSTRACT 11
1. Introduction 13
1.1. Acute lung injury (ALI) 13
1.2. LPS-induced inflammation and oxidative stress 16
1.3. Plant homeo domain finger protein 16 (PHF16; JADE3) 19
2. Materials and Methods 21
2.1. Mice 21
2.2. Preparation of cigarette smoke extract (CSE) 21
2.3. Cell culture and treatment 21
2.4. Western blot (WB) 22
2.5. RNA isolation and quantitative real-time reverse transcription-polymerase chain reaction (qPCR) 22
2.6. LPS-induced ALI murine model 23
2.7. Bronchoalveolar lavage fluid (BALF) analysis 24
2.8. Histological analysis 24
2.9. Statistical analysis 24
3. Results 25
3.1. LPS-induced inflammatory biomarkers are increased in Phf16 KO MEFs than in WT MEFs. 25
3.2. Phf16 knockdown MEFs exposed to LPS increased inflammatory biomarkers than control MEFs 28
3.3. Phf16-deficient MEFs increased Ho-1 expression under oxidative stress than control MEFs 30
3.4. Immune cell infiltration of bronchoalveolar lavage fluid (BALF) was increased in Phf16 KO mice exposed to LPS 32
3.5. Phf16 KO mice are highly susceptible to LPS-induced ALI 34
3.6. Protein level of lung tissues of WT and Phf16 KO mice 36
4. Discussion 38
5. References 41
ABSTRACT IN KOREAN 46
Figure 1. The pathology and cellular characterization of ALI 15
Figure 2. LPS-induced inflammatory and oxidative stress responses that... 18
Figure 3. The roles of PHF16... 20
Figure 4. Increased pro-inflammation cytokines in Phf16 KO MEFs exposed... 26
Figure 5. Increased activation of inflammation signaling mediators in Phf16... 27
Figure 6. Increased expression of pro-inflammation cytokines and activation... 29
Figure 7. Increased Ho-1 in Phf16-deficient MEFs exposed to H₂O₂ / CSE... 31
Figure 8. Analysis of immune cell infiltration in the bronchoalveolar lavage... 33
Figure 9. Analysis of lung tissues stained by hematoxylin and eosin (H&E)... 35
Figure 10. WB analysis of STAT3 phosphorylation and Ho-1 expression in... 37
Figure 11. Graphic abstract of this study 39