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In vivo and in vitro immunomodulation of Bambusae caulis in Liquamen on atopic dermatitis

Title
In vivo and in vitro immunomodulation of Bambusae caulis in Liquamen on atopic dermatitis
Other Titles
죽력(Bambusae caulis in Liquamen)의 아토피피부염에 대한 면역조절작용
Issue Date
2010
Publisher
Graduate School, Yonsei University
Description
Dept. of Medicine/박사
Abstract
[한글]
[영문]Background: Bambusae caulis in Liquamen (BCL) is a nutritious liquid extracted from heat-treated fresh bamboo stems. It is an important traditional herbal medicine used to treat coughs and asthma in East Asia. In recent years, it has been studied for its anti-inflammatory, anti-allergenic, immune-regulating, and antioxidant properties. Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by Th2-skewed immune response. However, in vivo and in vitro immunologic impacts and mechanisms of BCL on atopic dermatitis remain unknown. Aim of the study: (1) to examine whether BCL suppresses the development of 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in hairless mice; (2) to define whether and how BCL affects the expression of thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC), the Th2-type chemokines which are correlated with the disease severity in AD patients, in HaCaT keratinocytes. Materials and methods: First, the in vivo immunotherapeutic effects of BCL were analyzed using DNCB-induced hairless mice model by measuring transepidermal water loss (TEWL), melanin index, and erythema in the skin, leukocyte numbers and IgE levels in the serum, and mRNA expression of relevant cytokines in the spleen. Next, to verify the impacts of BCL on TARC and MDC expression in HaCaT cells and their potential mechanisms, we adopted a cell viability assay, RT-PCR, Real-time PCR, enzyme-linked immunosorbent assay (ELISA), Western blotting analysis, immunocytochemistry, DPPH analysis, and DCFH-DA analysis. Results: We found that topical application of BCL on hairless mice skin inhibited the development of DNCB-induced AD-like skin lesions by suppressing TEWL, erythema of skin, the number of leukocytes and the level of IgE in serum, and the mRNA expression of IL-4, IL-13, and TNF-α in the spleen. However, topical BCL treatment increased the expression of IFN-γ in the spleen. In addition, in vitro study showed that both Janus family kinases (JAKs)/p38 mitogen-activated kinase (MAPK) pathway and increase in intracellular reactive oxygen species (ROS) generation contributed separately to IFN-γ-induced production of TARC and MDC by activating nuclear factor-kappa B (NF-кB) signaling. However, BCL suppressed IFN-γ-induced expression of TARC and MDC by inhibiting the activation of ROS/IкB/NF-кB signaling due to its antioxidant effects. Although p38 MAPK also contributed to the expression of chemokines, BCL had minimal effects on phosphorylation of p38 MAPK. Conclusions: Taken together, in vivo findings indicate that BCL suppresses the development of DNCB-induced AD-like skin lesions in hairless mice. Additionally, in vitro findings indicate that intracellular ROS and JAKs/p38 MAPK independently contribute to IFN-γ-stimulated production of TARC and MDC by increasing NF-кB activation in HaCaT keratinocytes. BCL suppressed the production of TARC and MDC via inhibiting ROS/IкB/NF-кB pathways due to its antioxidant function. Collectively, this study suggests that BCL may be useful for AD treatment.
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/133417
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
Yonsei Authors
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