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Molecular markers of chronic inflammation and apoptosis in inflammatory bowel diseases

dc.contributor.advisorNikčević, Gordana
dc.contributor.otherPavlović, Sonja
dc.contributor.otherBrajušković, Goran
dc.contributor.otherNikčević, Gordana
dc.contributor.otherPavlović, Sonja
dc.creatorStanković, Biljana B.
dc.date.accessioned2020-07-03T08:07:29Z
dc.date.available2020-07-03T08:07:29Z
dc.date.issued2015-07-06
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/4171
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=2312
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:10223/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024962482
dc.description.abstractHronične inflamatorne bolesti creva (HIBC) predstavljaju rastući globalni zdravstveni problem, posebno u belim populacijama, uključujući i srpsku populaciju. Ova studija obuhvatila je dva tipa HIBC - inflamatornu bolest creva (IBC), koju čine Kronova bolest (KB) i ulcerozni kolitis (UK); i celijačnu bolest (CB). HIBC su kompleksne bolesti u čijoj, još uvek potpuno nerazjašnjenoj etiologiji učestvuju genetički, sredinski i imunološki faktori. Razvoj IBC je rezultat poremećenog imunološkog odgovora na crevnu mikrofloru kod genetički podložnih osoba. Ustanovljen je veliki broj asocijacija između IBC i varijanti u genima čiji proteinski produkti učestvuju u nespecifičnom imunskom odgovoru. Oštećenje intestinalne mukoze kod pacijenata sa IBC dešava se kao posledica deregulacije inflamatornih i apoptotskih procesa koji utiču na dugovečnost T ćelija i integritet epitelijalne barijere. Protein NF-κB je jedan od ključnih regulatora transkripcije gena eksprimiranih tokom ovih patogenetskih promena. U mukozi pacijenata sa KB dolazi do formiranja granuloma, limfoidnih mikrostruktura karakterističnih i za druge inflamatorne bolesti, među kojima je reumatoidni artritis (RA). Zbog toga su KB i RA klasifikovane kao granulomatozne bolesti. U poređenju sa brojnim, još uvek nedovoljno definisanim genetičkim faktorima rizika za razvoj IBC, nasledna komponenta u razvoju CB je dobro okarakterisana i najviše je povezana sa specifičnim varijantama gena HLA-DQ. Jedan od ciljeva ove studije je bio da ispita asocijaciju između HIBC i određenih genetičkih varijanti. Tačnije, analizirana je povezanost IBC sa varijantama u genima NOD2, TLR4, TNF-α, IL-6, IL-1β i IL-1RN, i ispitan je njihov prediktivni značaj za pojavu IBC. Varijanta u genu IL-6 ispitana je kao faktor rizika za nastanak dve granulomatozne bolesti, KB i RA. Takođe, analizirana je distribucija genotipova HLA-DQ u grupi pedijatrijskih pacijenata obolelih od CB i procenjen je rizik za pojavu CB koju ovi genotipovi nose. Sledeći cilj je bila analiza nivoa transkripcije proinflamatornih gena IL-6 i TNF-α, i apoptotskih gena Bcl-2, Bax, Fas i FasL u intestinalnoj mukozi i perifernoj krvi pacijenata obolelih od KB, kako bi se definisali ekspresioni profili gena uključenih u patogenezu KB i ispitao njihov dijagnostički potencijal. Poslednji cilj u okviru istaživanja vezanog za IBC odnosio se na analizu DNK vezujuće aktivnosti NF-κB iz jedarnih ekstrakata intestinalne mukoze pacijenata obolelih od KB...sr
dc.description.abstractChronic inflammatory bowel diseases (CIBDs) remain an expanding global health problem, particularly in most Caucasian populations, including Serbian. The focus of this study included two types of chronic inflammatory bowel diseases - inflammatory bowel disease (IBD), which comprises Crohn’s disease (CrD) and ulcerative colitis (UC); and celiac disease (CD). These are complex diseases with various genetic, environmental and immunological risk factors, whose etiologies are not yet fully resolved. The development of IBD is a result of abnormal immune response that occurs in genetically susceptible individuals against the enteric flora. Many studies have investigated associations between IBD occurrence and variants in genes that encode proteins involved in nonspecific immune response. Intestinal mucosal damage in CrD patients occurs as a result of the deregulation of inflammatory and apoptotic processes, which influence T cell longevity and epithelial barrier integrity. Regulatory protein NF-κB has a key role in the transcription of genes whose products are involved in these pathogenic events. Another property of CrD is formation of granulomas, which can also occur in other diseases, such as rheumatoid arthritis (RA). For that reason, CrD and RA are categorized as granulomatous diseases. Compared with numerous, still insufficiently defined genetic risk factors for the development of IBD, a genetic component in CD development is well characterized and mostly associated with specific variants of HLA-DQ genes. One of the aims of this study was to evaluate disease-gene associations. More precisely, we examined IBD associations with several genetic variants - variants in NOD2, TLR4, TNF-α, IL-6, IL-1β and IL-1RN genes, and investigated their contribution in the prediction of IBD occurrence. Additionally, we analyzed variant in IL-6 gene as a risk factor for two types of granulomatous diseases, CrD and RA. Also, we inspected the distribution of HLA-DQ genotypes in the group of pediatric celiac patients and estimated the risk of CD development that these genotypes confer. Another aim was the analysis of mRNA level of proinflammatory IL-6 and TNF-α, and apoptotic Bcl-2, Bax, Fas and FasL genes in intestinal mucosa, as well as in the peripheral blood of CrD patients, in order to reveal the expression patterns involved in the pathogenesis of CrD...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41004/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/143051/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjecthronične inflamatorne bolesti crevasr
dc.subjectchronic inflammatory bowel diseasesen
dc.subjectCrohn’s diseaseen
dc.subjectulcerative colitisen
dc.subjectceliac diseaseen
dc.subjectgranulomatous diseasesen
dc.subjectproinflammatory genesen
dc.subjectapoptotic genesen
dc.subjectHLA-DQ allelesen
dc.subjectpredictive modelingen
dc.subjectNF-κBen
dc.subjectKronova bolestsr
dc.subjectulcerozni kolitissr
dc.subjectcelijačna bolestsr
dc.subjectgranulomatozne bolestisr
dc.subjectproinflamatorni genisr
dc.subjectapoptotski genisr
dc.subjectaleli HLADQsr
dc.subjectprediktivni modelisr
dc.subjectNF-κB.sr
dc.titleMolekularni markeri hronične inflamacije i apoptoze kod inflamatornih bolesti crevasr
dc.titleMolecular markers of chronic inflammation and apoptosis in inflammatory bowel diseasesen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractНикчевић, Гордана; Павловић, Соња; Брајушковић, Горан; Никчевић, Гордана; Павловић, Соња; Станковић, Биљана Б.; Молекуларни маркери хроничне инфламације и апоптозе код инфламаторних болести црева; Молекуларни маркери хроничне инфламације и апоптозе код инфламаторних болести црева;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1611/Biljana_Stankovic_Referat_BF.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1610/Disertacija76.pdf


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