Приказ основних података о дисертацији
Uloga Interleukina-23 u prevremenom razvoju emfizema pluća među HIV-1 + pušačima
The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers
dc.contributor.advisor | Mostarica-Stojković, Marija | |
dc.contributor.other | Kaner, Robert | |
dc.contributor.other | Milenković, Branislava | |
dc.contributor.other | Jovanović, Tanja | |
dc.contributor.other | Miljković, Đorđe | |
dc.creator | Barjaktarević, Igor Ž. | |
dc.date.accessioned | 2016-12-30T16:13:53Z | |
dc.date.available | 2016-12-30T16:13:53Z | |
dc.date.available | 2020-07-03T08:47:55Z | |
dc.date.issued | 2016-09-28 | |
dc.identifier.uri | http://eteze.bg.ac.rs/application/showtheses?thesesId=4394 | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/7358 | |
dc.identifier.uri | https://fedorabg.bg.ac.rs/fedora/get/o:14289/bdef:Content/download | |
dc.identifier.uri | http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48486927 | |
dc.description.abstract | Genska 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.abstract | Matrix 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.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Београду, Медицински факултет | sr |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Универзитет у Београду | sr |
dc.subject | HIV | sr |
dc.subject | HIV | en |
dc.subject | alveolarni makrofagi | sr |
dc.subject | interleukin-23 | sr |
dc.subject | matriks metaloproteinaza-9 | sr |
dc.subject | emfizem | sr |
dc.subject | T limfociti | sr |
dc.subject | Th-17 | sr |
dc.subject | alveolar macrophage | en |
dc.subject | Interleukin IL-23 | en |
dc.subject | matrix metalloproteinase MMP-9 | en |
dc.subject | emphysema | en |
dc.subject | T lymphocytes | en |
dc.subject | Th-17 | en |
dc.title | Uloga Interleukina-23 u prevremenom razvoju emfizema pluća među HIV-1 + pušačima | sr |
dc.title.alternative | The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers | en |
dc.type | doctoralThesis | en |
dc.rights.license | BY-NC-ND | |
dcterms.abstract | Мостарица-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.fulltext | http://nardus.mpn.gov.rs/bitstream/id/8893/Disertacija7167.pdf | |
dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/8892/Disertacija.pdf | |
dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/8893/Disertacija7167.pdf | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/8892/Disertacija.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_7358 |