Anti-allergic effects of natural compounds and nanotherapeutic materials on atopic dermatitis and asthma
- 주제(키워드) Atopic dermatitis , 3′-Sialyllactose , Tregs , Asthma , NOX4
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 Jung-Soon Mo
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 박사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034321
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Anti-allergic effects of natural compounds and nanotherapeutic materials on atopic dermatitis and asthma Atopic dermatitis and asthma are representative chronic allergic diseases. Allergic inflammation on the skin is called atopic dermatitis, whereas that in the bronchi is called asthma. Allergic reactions in different parts of the body are interconnected. Therefore, children with atopic dermatitis often develop asthma and allergic rhinitis sequentially or concurrently as they grow into adults. Despite ongoing research into treatments for atopic dermatitis and asthma, a complete cure remains to be developed, and only symptomatic or anti-inflammatory medications are currently prescribed. Therefore, this study focused on evaluating the potential of therapeutic candidates 3′-sialyllactose and Mitotracer for treating atopic dermatitis and asthma, respectively. Oral administration of the prebiotic 3′-sialyllactose alleviated atopic dermatitis symptoms in a mouse model by increasing regulatory T cells, which regulated the expression of cytokines produced by T helper 1 (Th1), Th2, and Th17 cells. This differentiation of regulatory T cells and reduction of inflammation were related to the regulation of the Bifidobacterium population. Next, Mitotracer, a Povidone- coated Prussian blue nanomaterial, alleviated inflammation and oxidative stress in asthma by inhibiting NOX4-induced reactive oxygen species (ROS) production. Specifically, administration of Mitotracer via aerosol inhalation improved asthma symptoms in a mouse model by reducing the production of ROS and expression of Th2 cytokines, pro-inflammatory cytokines, and immunoglobulin E expression. Thus, Mitotracer is a safe therapeutic agent with antioxidants and anti-inflammatory effects on allergic asthma. These findings suggest that novel therapeutic approaches using natural compounds and nanomaterials hold promise for treating various allergic diseases, including atopic dermatitis and asthma.
more목차
I. Introduction 1
1. Atopic dermatitis and asthma 1
2. AD and regulatory T cells 2
3. Treatment of AD 3
4. Reactive oxygen species and asthma 4
5. Treatment of asthma 5
6. Nanotherapeutic materials and asthma 6
7. Aim of this study 7
II. Material and Methods 9
Animals 9
Establishment of an AD mouse model with house dust mite and 1% 2,4-dinitrochlorobenzene 9
In vitro cytotoxicity assay 10
Quantitative reverse transcription-polymerase chain reaction 11
Enzyme-linked immunosorbent assay of IgE, IL-1β, IL-6 and TNF-α 13
Histochemical analysis 14
Immunofluorescence staining 14
Flow cytometry 15
T cell proliferation assay 15
Human lung tissues 16
Ovalbumin-induced allergic asthma model 17
In vivo toxicity study 18
Biodistribution study of Miotracer 18
Statistical analysis 18
III. Results 20
Part I_ Natural compound for atopic dermatitis treatment 20
3′-SL alleviates the progression of experimentally induced AD by inhibiting sensitization and elicitation 20
3′-SL suppresses IgE production and reduces the levels of pro-inflammatory cytokines in AD-induced mouse serum 32
3′-SL inhibits HDM and 1% DNCB-induced AD pathogenic cytokines by inactivating NF-κB in the ear 34
3′-SL alleviates the systemic immune response by inhibiting T cell activation 42
3′-SL promoted regulatory T cell differentiation 44
3′-SL administration enhances incidence of Bifidobacterium 49
PART Ⅱ_ Nanotherapeutic material for asthma treatment 52
NOX4 depletion attenuates OVA-induced asthma 52
Mitotracer is safe and biocompatible for aerosol treatment in vivo 59
Phenotypes are similar between OVA-induced mice inhaled with Mitotracer or depleted of NOX4 65
IV. Discussion 73
V. Reference 81
국문 초록 90
