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The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers

dc.contributor.advisorMostarica-Stojković, Marija
dc.contributor.otherKaner, Robert
dc.contributor.otherMilenković, Branislava
dc.contributor.otherJovanović, Tanja
dc.contributor.otherMiljković, Đorđe
dc.creatorBarjaktarević, Igor Ž.
dc.date.accessioned2016-12-30T16:13:53Z
dc.date.available2016-12-30T16:13:53Z
dc.date.available2020-07-03T08:47:55Z
dc.date.issued2016-09-28
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/7358
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=4394
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:14289/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48486927
dc.description.abstractGenska ekspresija matriks metaloproteinaze-9 (MMP-9) je pojačana u alveolarnim makrofagima (AM) HIV-1 pozitivnih pušača obolelih od emfizema pluća. Na osnovu podataka koji ukazuju da supernatant bronhoalveolarnog lavata u plućima HIV-1 pozitivnih pušača sadrži povišene koncentracije inflamatornih citokina u odnosu na ovu tečnost u plućima HIV-1 negativnih pušača, postavili smo hipotezu da povišene koncentracije inflamatornih citokina u populaciji HIV-1 pozitivnih pušača utiču na povišenje koncentracije metaloproteinaza, na taj način dovodeći do ranog razvoja emfizema pluća. Putem multicitokinske analize, analizirali smo supernatante bronhoalveolarnog lavata 5 različitih fenotipskih grupa: HIV-1 negativnih nepušača, HIV-1 negativnih pušača bez poremećaja disajnih puteva, HIV-1 negativnih pušača sa ranim emfizemom pluća, HIV-1 pozitivnih nepušača i HIV-1 pozitivnih pušača sa ranim emfizemom pluća. Pored pojačane ekspresije inflamatornih citokina u plućima pušača zaraženih virusom HIV-1, povišene vrednosti citokina koji indukuju Th-17, pre svega interleukina IL-23, predstavljaju zajedničku karakteristiku HIV-1 pozitivnih nepušača, HIV-1 pozitivnih pušača sa ranim emfizemom pluća i HIV-1 negativnih pušača sa ranim emfizemom pluća. Relativna ekspresija IL-23 gena u AM HIV-1 pozitivnih osoba je povišena u odnosu na AM HIV-1 negativnih ispitanika, i značajno je povišena u odnosu na AM HIV-1 pozitivnih pušača sa ranim emfizemom pluća. Akutna infekcija HIV-1 virusom in vitro dovodi do pojačane ekspresije IL-23 u HIV-1 negativnim AM. Stimulacija kultura AM IL-23 dovodi do pojačane ekspresije MMP-9 gena i pojačane koncentracije MMP-9. S obzirom na to da AM zdravih osoba ne eksprimiraju IL-23 receptor (IL-23R), činjenice da kulture makrofaga prečišćenih adherencijom sadrže izvestan procenat T limfocita i činjenice da dodavanje T limfocita ovim kulturama pojačava produkciju MMP-9, efekat IL-23 na pojačano lučenje MMP-9 može biti indirektan i zahteva učešće T limfocita u ovom procesu...sr
dc.description.abstractMatrix metalloproteinase-9 (MMP-9) is up-regulated in alveolar macrophages (AM) of HIV1+ smokers, who develop emphysema in an accelerated time frame compared to HIV1- smokers. The epithelial lining fluid (ELF) of HIV1+ smokers has increased levels of inflammatory cytokines compared to their HIV1- counterparts. To assess the hypothesis that up-regulation of lung cytokines may be functionally related to the increased concentrations of MMP-9, arrays were used to evaluate relative cytokine protein levels in the ELF obtained from 5 groups of individuals: HIV1‾ healthy nonsmokers, HIV1‾ healthy smokers, HIV1‾ smokers with early emphysema, HIV1 + nonsmokers, and HIV1 + smokers with early emphysema. While several proinflammatory cytokines were increased in smoking and HIV1+ phenotypes, increased levels of Th17-related cytokines such as IL-23 and IL-17 represented a common finding in HIV1- smokers with early emphysema as well as in HIV1+ individuals independently of their smoking history. We further hypothesized that IL-23 is up-regulated in the setting of HIV1 infection and that this pro-inflammatory cytokine may be directly correlated to increased concentrations of MMP-9 in the ELF of HIV1+ smokers with early emphysema. Relative gene expression of AM IL-23 is significantly increased in HIV1+ individuals, with a trend toward even greater expression in HIV1+ smokers with early emphysema. Infection with HIV1 laboratory strain JRFL in vitro induced IL-23 expression in normal AM. With the knowledge that AM cultured by the adherence method contain a small number of other cells, including lymphocytes, we hypothesized that in an AM/lymphocyte co-culture system IL-23 would up-regulate MMP-9. Stimulation of AM/lymphocyte co-cultures with IL-23 in vitro induced increased MMP-9 gene expression and protein. While AM obtained from healthy individuals do not express IL-23 receptors, T lymphocytes express IL-23R and act as an intermediary to up-regulate AM MMP-9...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectHIVsr
dc.subjectHIVen
dc.subjectalveolarni makrofagisr
dc.subjectinterleukin-23sr
dc.subjectmatriks metaloproteinaza-9sr
dc.subjectemfizemsr
dc.subjectT limfocitisr
dc.subjectTh-17sr
dc.subjectalveolar macrophageen
dc.subjectInterleukin IL-23en
dc.subjectmatrix metalloproteinase MMP-9en
dc.subjectemphysemaen
dc.subjectT lymphocytesen
dc.subjectTh-17en
dc.titleUloga Interleukina-23 u prevremenom razvoju emfizema pluća među HIV-1 + pušačimasr
dc.title.alternativeThe Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokersen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractМостарица-Стојковић, Марија; Миљковић, Ђорђе; Канер, Роберт; Јовановић, Тања; Миленковић, Бранислава; Барјактаревић, Игор Ж.; Улога Интерлеукина-23 у превременом развоју емфизема плућа међу ХИВ-1 + пушачима; Улога Интерлеукина-23 у превременом развоју емфизема плућа међу ХИВ-1 + пушачима;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/8893/Disertacija7167.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/8892/Disertacija.pdf


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