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The utilization of drug repositioning in allergic disease

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dc.contributor.author김, 서희-
dc.date.accessioned2023-11-16T05:43:55Z-
dc.date.available2023-11-16T05:43:55Z-
dc.date.issued2023-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/26840-
dc.language.isoen-
dc.titleThe utilization of drug repositioning in allergic disease-
dc.title.alternative알레르기 질환에서 약물 재창출의 활용-
dc.typeThesis-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000032714-
dc.subject.keywordAsthma-
dc.subject.keywordEosinophil-
dc.subject.keywordTirofiban-
dc.subject.keywordPhthalate-
dc.subject.keywordFlavonoid-
dc.subject.keyword천식-
dc.subject.keyword호산구-
dc.subject.keyword환경호르몬-
dc.description.degreeDoctor-
dc.contributor.department대학원 의생명과학과-
dc.contributor.affiliatedAuthor김, 서희-
dc.date.awarded2023-
dc.type.localTheses-
dc.citation.date2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.description.tableOfContentsThe effect of tirofiban on the mouse model of asthma 1

I. INTRODUCTION 2

II. MATERIALS AND METHODS 4

A. Mouse 4

B. Ethics statement· 4

C. Eosinophilic asthma mouse model and tirofiban treatment 4

D. Measurement of airway resistance and sample collection 4

E. Harvest of the BALF and measurement of differential cell counts 5

F. Measurement of cytokine levels 5

G. Identification of platelet eosinophil aggregation (PEA) in whole blood 5

H. Detection MAC-1 of by western blotting 6

I. Immunofluorescence staining 6

J. Antibodies and reagents 7

K. Statistical analysis 7

III. RESULTS 8

A. The effects of tirofiban on airway resistance and inflammation 8

B. Staining in the lung tissues 9

C. The percentage of PEA in whole blood of mice 10

D. Tirofiban inhibits both platelet and eosinophil activation in the BALF 11

E. The levels of EPX and PSGL-1 in the lung tissues 11

F. Tirofiban decreases adhesion molecules on eosinophil surface 12

IV. DISCUSSION 14

The effect of phthalates as an aggravating factor on allergic diseases 16

I. INTRODUCTION 17

II. MATERIALS AND METHODS 19

A. Mouse 19

B. Eosinophilic asthma mouse model, MnBP and apigenin treatment 19

C. Evaluation of airway resistance, cytokines in the BALF, and the lung histology 20

D. Western blotting to detect aryl hydrocarbon receptor and eosinophilic granular proteins 20

E. cDNA preparation and real time polymerase chain reaction 21

F. Mononuclear cell isolation and ex vivo cytokines measurement 21

G. In vitro cells preparation and culture 21

H. A549 cell by siRNA transfection 22

I. Measurement on β-hexosaminidase release in LAD2 cells 22

J. Measurement of phthalates in urine of patients with chronic urticaria and healthy controls 23

K. Statistical analysis 24

III. RESULTS 25

A. The expression of aryl hydrocarbon receptor in the MnBP-treated allergic asthma 25

B. The effects of MnBP and apigenin on allergic asthma mouse 26

C. The effects of MnBP and apigenin on eosinophilic activation on allergic mouse model 28

D. Ex vivo effects of MnBP and apigenin on type II cytokine productions on the splenic MNCs 29

E. In vitro effects of MnBP and apigenin on type II cytokine productions using Jurkat cells 30

F. The effects of MnBP and apigenin on eosinophilic activation on Eol-1 cells 30

G. The inhibitory effects of aryl hydrocarbon receptor using siRNA and its antagonist in vitro epithelial cells 31

H. Stimulatory effects of beta-hexosaminidase release on phthalates stimulated LAD 2 cells 32

I. The comparison of concentrations of phthalate metabolites in urine 33

IV. DISCUSSION 35

V. CONCLUSION 39

REFERENCES 40

국문요약 49
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