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Role of Fucosyltransferase 1 in inflammatory skin responses

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Authors
김경현
Advisor
정진호
Major
의과대학 의과학과
Issue Date
2014-08
Publisher
서울대학교 대학원
Keywords
Ultraviolet radiationTPAinflammationFUT1cell adhesion molecules
Description
학위논문 (석사)-- 서울대학교 대학원 : 의과학과, 2014. 8. 정진호.
Abstract
ABH antigens are representative terminal structures of glycan chain. Since the discovery of ABO blood groups on human erythrocytes by Karl Landsteiner, it has been found that ABH antigens are also present in biological fluids and various tissues including skin. ABH antigens are synthesized from the addition of monosaccharide units to the H precursors in a step-wise manner. To be more specific, H antigen synthesis requires the addition of a fucose onto precursors and the catalysis of this reaction by α-1,2-fucosyltransferase 1 (FUT1). After having synthesized H antigen, A and B antigens can be made by adding corresponding sugars to H antigen. It has been elucidated that FUT1 is over-expressed or under-expressed in some cancers and has an important role in tumor growth and metastasis. Moreover, FUT1 has also been found to mediate angiogenesis and inflammatory cell adhesion. Ultraviolet light (UV) exposure on skin can cause acute skin inflammation as well as photodamage and skin tumors. The Oxazolone is the chemical that induces allergic contact dermatitis (ACD). The 12-O-tetradecanoylphorbol 13-acetate (TPA) is the chemical that induces skin inflammation which can represent a model of irritant contact dermatitis (ICD). The mechanisms of UV or chemicals such as oxazolone and TPA induced skin damage and inflammatory responses have been widely characterized. However, the role of FUT1 in these kinds of skin inflammation model has yet to be determined. First, I compared the UV-induced inflammatory responses between FUT1 KO and wild type mice. CD45-positive inflammatory cells were significantly more recruited in UV-irradiated skin of FUT1 KO mice. Because no significant difference between FUT1 KO mice and its wild type littermates was detected in the double immunofluorescent staining with CD31, a blood vessel marker, and CD45, more infiltration of CD45-positive cells into the skin is independent of extravasation. UV-induced pro-inflammatory cytokine, IL-1β, was significantly augmented in FUT1 KO mice when compared to wild type mice. Anti-inflammatory cytokine, IL-10, did not show any differences between two genotypes. VEGF and ICAM-1, known to be previously associated with FUT1, were also evaluated. Although the level of VEGF did not show any differences between the two genotypes, the levels of UV-induced ICAM-1 were significantly increased in FUT1 KO mice, compared to wild type littermates. These results indicate that mice deficient in FUT1 are more susceptible to UV-induced inflammation. Next, by using oxazolone-induced allergic contact dermatitis model and TPA-induced irritant contact dermatitis model, I found that mice deficient in FUT1 KO showed different responses with wild type mice. Oxazolone-induced immune cell infiltration were more increased in FUT1 KO mice. TPA-induced ICAM-1 expression in the epidermis was highly decreased in FUT1 KO mice compared to that of the wild type littermates. Further studies using two types of contact dermatitis model should be conducted for exact results. In conclusion, FUT1 deficiency can have an effect on skin inflammation in vivo, suggesting the complex role of FUT1 in the context of distinct inflammatory conditions.
Language
English
URI
http://hdl.handle.net/10371/133000
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Master's Degree_의과학과)
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