Uloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbiji
Roles of polymorphisms and expression of genes coding for chemokines CX3C ligand 1 and CXC ligand 16 and their receptors in the development and progression of multiple sclerosis in Serbia
Аутори
Stojković, Ljiljana S.Остала ауторства
Živković, MajaSavić-Pavićević, Dušanka
Dinčić, Evica
Докторска теза
Метаподаци
Приказ свих података о документуАпстракт
Multipla skleroza je hroniĉna inflamatorna, autoimunska, demijelinizaciona ineurodegenerativna bolest centralnog nervnog sistema (CNS-a). Hemokini i njihovireceptori predstavljaju znaĉajne medijatore inflamacije koji uĉestvuju u patogeneziodreĊenih hroniĉnih inflamatornih i autoimunskih bolesti meĊu kojima je i multiplaskleroza. Ciljni hemokini u ovoj studiji, CX3C ligand 1 (CX3CL1) i CXC ligand 16(CXCL16), specifiĉni su po tome što postoje u dve forme - kao transmembranskiadhezivni molekuli i kao solubilni hemoatraktanti koji nastaju nakon proteolitiĉkogseĉenja vanćelijskih hemokinskih domena njihovih transmembranskih formi. U tokuinflamatornog odgovora, na membrani endotelnih vaskularnih ćelija eksprimirani suCX3CL1 i CXCL16, a na membrani leukocita receptori za CX3CL1 (CX3CR1) iCXCL16 (CXCR6), te ovi hemokini i njihovi receptori posreduju u prodiranju leukocitaiz krvi u tkivo zahvaćeno inflamacijom, podsticanjem hemotaksije i adhezije leukocitaza aktivirani endotel krvnog suda.Ova s...tudija obuhvata genetsko-epidemiološku analizu polimorfizama zamenapojedinaĉnih nukleotida u kodirajućim regionima gena, koje rezultuju zamenamaaminokiselina. To su polimorfizmi V249I i T280M u genu za CX3CR1, i I123T iA181V u genu za CXCL16. U prethodnim studijama je pokazano da ovi genskipolimorfizmi menjaju funkcionalna svojstva CX3CR1 i CXCL16, kao i da su asociranisa patogenezom odreĊenih hroniĉnih inflamatornih bolesti. Uzimajući to u obzir, ovastudija je imala za cilj da po prvi put ispita asocijaciju navedenih polimorfizama ugenima za CX3CR1 i CXCL16 sa nastankom i progresijom multiple skleroze.Primenom alel-specifiĉne PCR metode i PIRA PCR-RFLP metode detektovani sugenotipovi polimorfizama V249I i T280M u genu za CX3CR1, kod zdravih kontrola ipacijenata sa multiplom sklerozom. UtvrĊeno je da haplotip I249T280 u genu za CX3CR1ima znaĉajno veću uĉestalost kod pacijenata sa relapsno-remitentnom (RR) formom, u odnosu na pacijente sa sekundarno-progresivnom (SP) formom multiple skleroze, štoznaĉi da ovaj haplotip ima protektivni efekat na progresiju RR u SP formu bolesti...
Multiple sclerosis is a chronic inflammatory, autoimmune, demyelinating andneurodegenerative disease of the central nervous system (CNS). Chemokines and theirreceptors are important mediators of inflammation, which are involved in pathogenesisof certain chronic inflammatory and autoimmune diseases including multiple sclerosis.Chemokines of interest in this study, CX3C ligand 1 (CX3CL1) and CXC ligand 16(CXCL16), are specific in that they can exist either as transmembrane adhesionmolecules or soluble chemoattractants being generated by proteolytic cleavage of theirtransmembrane forms’ extracellular domains. During the inflammatory response,CX3CL1 and CXCL16 are expressed on the surface of vascular endothelium, while theleukocytes produce membrane receptors for CX3CL1 (CX3CR1) and CXCL16(CXCR6). Therefore, these chemokines and their receptors mediate the infiltration ofleukocytes from blood into the inflamed tissue areas, by stimulation of both chemotaxisand adhesion of leukocytes to the... activated endothelium of blood vessels.This study is based on genetic epidemiological analysis of single nucleotidepolymorphisms, which are located in the coding regions of genes and result in aminoacids’ substitutions. These are V249I and T280M substitutions in the gene coding forCX3CR1, and I123T and A181V substitutions in the gene coding for CXCL16. Inprevious studies these polymorphisms have been associated with the functionalproperties of CX3CR1 and CXCL16 as well as the pathogenesis of certain chronicinflammatory diseases. Therefore, this study aimed to investigate the association of thepolymorphisms in CX3CR1 and CXCL16 genes with the development and progressionof multiple sclerosis. Using the allele-specific PCR and PIRA PCR-RFLP methods,genotypes of CX3CR1 V249I and T280M polymorphisms were detected in healthycontrols and patients with multiple sclerosis. Following statistical analysis showedsignificantly higher frequency of CX3CR1 I249T280 haplotype in patients with relapsingremitting(RR) form, compared to patients with secondary-progressive (SP) form of multiple sclerosis, so this haplotype had a protective effect on progression of RR to SPform of the disease...
Кључне речи:
multipla skleroza / multiple sclerosis / gene / polymorphism / expression / chemokine / CX3CL1 / CXCL16 / CX3CR1 / CXCR6 / gen / polimorfizam / ekspresija / hemokin / CX3CL1 / CXCL16 / CX3CR1 / CXCR6Извор:
Универзитет у Београду, 2013Издавач:
- Универзитет у Београду, Биолошки факултет
Финансирање / пројекти:
- Интегрална студија идентификације регионалних генетских фактора ризика и фактора ризика животне средине за масовне незаразне болести хумане популације у Србији - INGEMA_S (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41028)
- Генетска основа хуманих васкуларних и инфламаторних болести (RS-MESTD-Basic Research (BR or ON)-175085)
URI
http://eteze.bg.ac.rs/application/showtheses?thesesId=1108https://fedorabg.bg.ac.rs/fedora/get/o:7848/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024587442
http://nardus.mpn.gov.rs/123456789/2155
https://vinar.vin.bg.ac.rs/handle/123456789/7242
Колекције
Институција/група
VinčaTY - THES AU - Stojković, Ljiljana S. PY - 2013 UR - http://eteze.bg.ac.rs/application/showtheses?thesesId=1108 UR - https://fedorabg.bg.ac.rs/fedora/get/o:7848/bdef:Content/download UR - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024587442 UR - http://nardus.mpn.gov.rs/123456789/2155 UR - https://vinar.vin.bg.ac.rs/handle/123456789/7242 AB - Multipla skleroza je hroniĉna inflamatorna, autoimunska, demijelinizaciona ineurodegenerativna bolest centralnog nervnog sistema (CNS-a). Hemokini i njihovireceptori predstavljaju znaĉajne medijatore inflamacije koji uĉestvuju u patogeneziodreĊenih hroniĉnih inflamatornih i autoimunskih bolesti meĊu kojima je i multiplaskleroza. Ciljni hemokini u ovoj studiji, CX3C ligand 1 (CX3CL1) i CXC ligand 16(CXCL16), specifiĉni su po tome što postoje u dve forme - kao transmembranskiadhezivni molekuli i kao solubilni hemoatraktanti koji nastaju nakon proteolitiĉkogseĉenja vanćelijskih hemokinskih domena njihovih transmembranskih formi. U tokuinflamatornog odgovora, na membrani endotelnih vaskularnih ćelija eksprimirani suCX3CL1 i CXCL16, a na membrani leukocita receptori za CX3CL1 (CX3CR1) iCXCL16 (CXCR6), te ovi hemokini i njihovi receptori posreduju u prodiranju leukocitaiz krvi u tkivo zahvaćeno inflamacijom, podsticanjem hemotaksije i adhezije leukocitaza aktivirani endotel krvnog suda.Ova studija obuhvata genetsko-epidemiološku analizu polimorfizama zamenapojedinaĉnih nukleotida u kodirajućim regionima gena, koje rezultuju zamenamaaminokiselina. To su polimorfizmi V249I i T280M u genu za CX3CR1, i I123T iA181V u genu za CXCL16. U prethodnim studijama je pokazano da ovi genskipolimorfizmi menjaju funkcionalna svojstva CX3CR1 i CXCL16, kao i da su asociranisa patogenezom odreĊenih hroniĉnih inflamatornih bolesti. Uzimajući to u obzir, ovastudija je imala za cilj da po prvi put ispita asocijaciju navedenih polimorfizama ugenima za CX3CR1 i CXCL16 sa nastankom i progresijom multiple skleroze.Primenom alel-specifiĉne PCR metode i PIRA PCR-RFLP metode detektovani sugenotipovi polimorfizama V249I i T280M u genu za CX3CR1, kod zdravih kontrola ipacijenata sa multiplom sklerozom. UtvrĊeno je da haplotip I249T280 u genu za CX3CR1ima znaĉajno veću uĉestalost kod pacijenata sa relapsno-remitentnom (RR) formom, u odnosu na pacijente sa sekundarno-progresivnom (SP) formom multiple skleroze, štoznaĉi da ovaj haplotip ima protektivni efekat na progresiju RR u SP formu bolesti... AB - Multiple sclerosis is a chronic inflammatory, autoimmune, demyelinating andneurodegenerative disease of the central nervous system (CNS). Chemokines and theirreceptors are important mediators of inflammation, which are involved in pathogenesisof certain chronic inflammatory and autoimmune diseases including multiple sclerosis.Chemokines of interest in this study, CX3C ligand 1 (CX3CL1) and CXC ligand 16(CXCL16), are specific in that they can exist either as transmembrane adhesionmolecules or soluble chemoattractants being generated by proteolytic cleavage of theirtransmembrane forms’ extracellular domains. During the inflammatory response,CX3CL1 and CXCL16 are expressed on the surface of vascular endothelium, while theleukocytes produce membrane receptors for CX3CL1 (CX3CR1) and CXCL16(CXCR6). Therefore, these chemokines and their receptors mediate the infiltration ofleukocytes from blood into the inflamed tissue areas, by stimulation of both chemotaxisand adhesion of leukocytes to the activated endothelium of blood vessels.This study is based on genetic epidemiological analysis of single nucleotidepolymorphisms, which are located in the coding regions of genes and result in aminoacids’ substitutions. These are V249I and T280M substitutions in the gene coding forCX3CR1, and I123T and A181V substitutions in the gene coding for CXCL16. Inprevious studies these polymorphisms have been associated with the functionalproperties of CX3CR1 and CXCL16 as well as the pathogenesis of certain chronicinflammatory diseases. Therefore, this study aimed to investigate the association of thepolymorphisms in CX3CR1 and CXCL16 genes with the development and progressionof multiple sclerosis. Using the allele-specific PCR and PIRA PCR-RFLP methods,genotypes of CX3CR1 V249I and T280M polymorphisms were detected in healthycontrols and patients with multiple sclerosis. Following statistical analysis showedsignificantly higher frequency of CX3CR1 I249T280 haplotype in patients with relapsingremitting(RR) form, compared to patients with secondary-progressive (SP) form of multiple sclerosis, so this haplotype had a protective effect on progression of RR to SPform of the disease... PB - Универзитет у Београду, Биолошки факултет T2 - Универзитет у Београду T1 - Uloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbiji T1 - Roles of polymorphisms and expression of genes coding for chemokines CX3C ligand 1 and CXC ligand 16 and their receptors in the development and progression of multiple sclerosis in Serbia UR - https://hdl.handle.net/21.15107/rcub_nardus_2155 ER -
@phdthesis{ author = "Stojković, Ljiljana S.", year = "2013", abstract = "Multipla skleroza je hroniĉna inflamatorna, autoimunska, demijelinizaciona ineurodegenerativna bolest centralnog nervnog sistema (CNS-a). Hemokini i njihovireceptori predstavljaju znaĉajne medijatore inflamacije koji uĉestvuju u patogeneziodreĊenih hroniĉnih inflamatornih i autoimunskih bolesti meĊu kojima je i multiplaskleroza. Ciljni hemokini u ovoj studiji, CX3C ligand 1 (CX3CL1) i CXC ligand 16(CXCL16), specifiĉni su po tome što postoje u dve forme - kao transmembranskiadhezivni molekuli i kao solubilni hemoatraktanti koji nastaju nakon proteolitiĉkogseĉenja vanćelijskih hemokinskih domena njihovih transmembranskih formi. U tokuinflamatornog odgovora, na membrani endotelnih vaskularnih ćelija eksprimirani suCX3CL1 i CXCL16, a na membrani leukocita receptori za CX3CL1 (CX3CR1) iCXCL16 (CXCR6), te ovi hemokini i njihovi receptori posreduju u prodiranju leukocitaiz krvi u tkivo zahvaćeno inflamacijom, podsticanjem hemotaksije i adhezije leukocitaza aktivirani endotel krvnog suda.Ova studija obuhvata genetsko-epidemiološku analizu polimorfizama zamenapojedinaĉnih nukleotida u kodirajućim regionima gena, koje rezultuju zamenamaaminokiselina. To su polimorfizmi V249I i T280M u genu za CX3CR1, i I123T iA181V u genu za CXCL16. U prethodnim studijama je pokazano da ovi genskipolimorfizmi menjaju funkcionalna svojstva CX3CR1 i CXCL16, kao i da su asociranisa patogenezom odreĊenih hroniĉnih inflamatornih bolesti. Uzimajući to u obzir, ovastudija je imala za cilj da po prvi put ispita asocijaciju navedenih polimorfizama ugenima za CX3CR1 i CXCL16 sa nastankom i progresijom multiple skleroze.Primenom alel-specifiĉne PCR metode i PIRA PCR-RFLP metode detektovani sugenotipovi polimorfizama V249I i T280M u genu za CX3CR1, kod zdravih kontrola ipacijenata sa multiplom sklerozom. UtvrĊeno je da haplotip I249T280 u genu za CX3CR1ima znaĉajno veću uĉestalost kod pacijenata sa relapsno-remitentnom (RR) formom, u odnosu na pacijente sa sekundarno-progresivnom (SP) formom multiple skleroze, štoznaĉi da ovaj haplotip ima protektivni efekat na progresiju RR u SP formu bolesti..., Multiple sclerosis is a chronic inflammatory, autoimmune, demyelinating andneurodegenerative disease of the central nervous system (CNS). Chemokines and theirreceptors are important mediators of inflammation, which are involved in pathogenesisof certain chronic inflammatory and autoimmune diseases including multiple sclerosis.Chemokines of interest in this study, CX3C ligand 1 (CX3CL1) and CXC ligand 16(CXCL16), are specific in that they can exist either as transmembrane adhesionmolecules or soluble chemoattractants being generated by proteolytic cleavage of theirtransmembrane forms’ extracellular domains. During the inflammatory response,CX3CL1 and CXCL16 are expressed on the surface of vascular endothelium, while theleukocytes produce membrane receptors for CX3CL1 (CX3CR1) and CXCL16(CXCR6). Therefore, these chemokines and their receptors mediate the infiltration ofleukocytes from blood into the inflamed tissue areas, by stimulation of both chemotaxisand adhesion of leukocytes to the activated endothelium of blood vessels.This study is based on genetic epidemiological analysis of single nucleotidepolymorphisms, which are located in the coding regions of genes and result in aminoacids’ substitutions. These are V249I and T280M substitutions in the gene coding forCX3CR1, and I123T and A181V substitutions in the gene coding for CXCL16. Inprevious studies these polymorphisms have been associated with the functionalproperties of CX3CR1 and CXCL16 as well as the pathogenesis of certain chronicinflammatory diseases. Therefore, this study aimed to investigate the association of thepolymorphisms in CX3CR1 and CXCL16 genes with the development and progressionof multiple sclerosis. Using the allele-specific PCR and PIRA PCR-RFLP methods,genotypes of CX3CR1 V249I and T280M polymorphisms were detected in healthycontrols and patients with multiple sclerosis. Following statistical analysis showedsignificantly higher frequency of CX3CR1 I249T280 haplotype in patients with relapsingremitting(RR) form, compared to patients with secondary-progressive (SP) form of multiple sclerosis, so this haplotype had a protective effect on progression of RR to SPform of the disease...", publisher = "Универзитет у Београду, Биолошки факултет", journal = "Универзитет у Београду", title = "Uloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbiji, Roles of polymorphisms and expression of genes coding for chemokines CX3C ligand 1 and CXC ligand 16 and their receptors in the development and progression of multiple sclerosis in Serbia", url = "https://hdl.handle.net/21.15107/rcub_nardus_2155" }
Stojković, L. S.. (2013). Uloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbiji. in Универзитет у Београду Универзитет у Београду, Биолошки факултет.. https://hdl.handle.net/21.15107/rcub_nardus_2155
Stojković LS. Uloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbiji. in Универзитет у Београду. 2013;. https://hdl.handle.net/21.15107/rcub_nardus_2155 .
Stojković, Ljiljana S., "Uloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbiji" in Универзитет у Београду (2013), https://hdl.handle.net/21.15107/rcub_nardus_2155 .