Atopijski dermatitis induciran analogom vitamina D3 na modelu miša

master's thesis

• Title (english): Atopic dermatitis induced with vitamin D analog on mouse model
• Author: Marija Nimac
• Mentor: Lidija Šver (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Biology and Microbial Genetics); Zagreb
• Defense date and country: 2015-02-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Atopijski dermatitis (AD) je kronično recidivirajuća upalna dermatoza obilježena svrbežom, suhoćom kože i tipičnom kliničkom slikom koja u značajnoj mjeri ovisi o dobi bolesnika. Genetska predispozicija, različiti okolišni čimbenici, osobitosti imunosnog odgovora domaćina, oštećena epidermalna barijera te mnogi drugi čimbenici pridonose razvoju bolesti. Istraživanja su pokazala kako vitamin D ima značajan utjecaj na aktiviranje signala koji dovode do sinteze citokina odgovornih za izazivanje alergijske upale koja podsjeća na AD. Cilj ovog rada bio je, na modelu miša, dokazati da lokalna primjena otopine analoga vitamina D (MC903) izaziva AD. Miševima pokusne skupine svakodnevno su deset dana tretirane uške otopinom MC903 u etanolu, a miševima kontrolne skupine etanolom. U pokusnoj skupini opisane su vanjske karakteristike svojstvene AD i utvrđena je povećana masa uški zbog povećane sinteze i infiltracije stanica odgovornih za upalnu reakciju. Također, histološki nalaz uški miševa pokusne skupine ukazuju na zadebljanje dermisa i povećan broj stanica ispod bazalne membrane. U drugom pokusu, miševi su tijekom deset dana svakodnevno tretirani otopinama te je svaki dan žrtvovan po jedan nasumično izdvojen miš iz pokusne i kontrolne skupine. Stanice uški ovih miševa poslužile su za analizu genskog izražaja TSLP-a te IL-4. U stanicama uški miševa iz pokusne skupine bila je povećana razina TSLP-a i IL-4. Različiti učinak vitamina D na pojavnost AD može se objasniti činjenicom da, ovisno o načinu primjene, vitamin D djeluje na različite populacije stanica; sistemska primjena vitamina D promovira regulacijske T stanice i DC a lokalna primjena stimulira keratinocite (i DC) na način da nadilazi imunosupresivni učinak vitamina D i promovira alergeni odgovor. Iz svega navedenog može se zaključiti da vitamin D ili njegov analog lokalno primjenjen na kožu izaziva AD.

Abstract (english)

Atopic dermatitis is chronic inflammatory disease characterized by severe itch and typical clinical picture. Besides genetic there are other factors such as the environmental influence, damaged barrier function and various other. Multiple studies have shown that vitamin D has influence on activation of signals that leads to synthesis of cytokine responsible for causing allergic inflammation that reminds on atopic dermatitis. The aim of this experiment was to prove atopic dermatitis induced with topical application of analogue of vitamin D (MC903) in mouse. Experimental group we treated with analogue of vitamin D (MC903) mixed with ethanol while the control group was treated with ethanol. All mice from experimental group developed characteristic AD-like phenotype. Weight of ears mice from experimental group was significantly higher compared to weight of ears mice from control group. Histologic analysis of ears mice from experimental group revealed epidermal hyperplasia and a heavy dermal cell infiltrate. In second experiment one randomly selected mouse from both groups was sacrified every day. Ears of mice from this experiment were used to analyze the gene expression of TSLP and IL-4. It was found increase gene expression of TSLP and IL-4 in cells of the mouse ears that were treated with MC903 mixed with ethanol while the cells of mouse ears treated with ethanol show no gene expression of TSLP and IL-4. Disparate effects of vitamin D result causing AD can be explained from differences in target cell populations. Systemically administered vitamin D can promote dendritic and regulatory T cell development, however, stimulation of keratinocytes (and dendritic cells) by topical application may override the immunosuppressive effects of vitamin D, thus promoting an allergic answer. Taken everything together we can conclude that topical application of vitamin D on skin can induce AD.

• Keywords: atopijski dermatitis; vitamin D; TSLP; VDR
• Keywords (english): atopic dermatitis; vitamin D; TSLP; VDR
• Language: croatian
• URN:NBN: urn:nbn:hr:159:754497
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-04-28 08:46:05