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035 a| (Sirsi) o1113942189;

035 a| (OCoLC)1113942189;

049 a| EREE;

100 1 a| Sanderford, Victoria L.,e| author.?| UNAUTHORIZED;

245 10 a| Peroxisome proliferator-activated receptor gamma deficiency promotes a T lymphocyte response in a murine model of chronic pulmonary sarcoidosis /c| by Victoria L. Sanderford.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2019.;

300 a| 91 pages :b| color illustrations.;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 2.065 MB2| rda;

490 1 a| ECU Brody School of Medicine thesis;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| M.S.c| East Carolina Universityd| 2019.;

500 a| Presented to the faculty of the MS Program in Biomedical Sciences;

500 a| Advisor: Arjun Mohan;

500 a| Title from PDF t.p. (viewed November 14, 2019).;

520 3 a| Sarcoidosis is a chronic granulomatous disease of unknown etiology. Previous studies from our lab have shown a deficiency of the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPAR[gamma]) in the alveolar macrophages of sarcoidosis patients. We established a murine model of granuloma formation by instillation with multiwall carbon nanotubes (MWCNT), and the expression of PPAR[gamma] was also decreased in MWCNT instilled mice. There is evidence linking lymphocyte reactivity to mycobacterial antigens in sarcoidosis, so we hypothesized that addition of mycobacterial peptide early secretory antigenic target 6 (ESAT-6) to MWCNT might exacerbate the murine T effector cell response. MWCNT with or without ESAT-6 peptide 14 were instilled into macrophage-specific PPAR[gamma]-KO or wild-type mice. Controls received vehicle or ESAT-6 alone. Bronchoalveolar lavage (BAL) fluid was collected for analysis via qPCR, and lymph nodes were collected for histology, qPCR, in vitro studies, or flow cytometric analysis. PPAR[gamma]-KO mice receiving MWCNT+ESAT-6 displayed markedly increased granuloma formation and exhibited mediastinal lymphadenopathy. Additionally, PPAR[gamma]-KO mice treated with MWCNT+ESAT-6 exhibited exacerbated fibrotic severity at 20- and 60- days post-instillation. Similarly, lymphocyte frequency was elevated in the BAL of PPAR[gamma]-KO mice compared to controls at 20- and 60-days post-instillation with MWCNT+ESAT-6. Further, TH17 associated transcription factor ROR[gamma]t and immune regulatory marker PD1 were elevated in PPAR[gamma]-KO mice treated with MWCNT+ESAT-6 compared to sham mice at both time points, with elevation of multiple other TH17 associated genes at 60 days post instillation. Carbon nanotubes were observed in the mediastinal lymph nodes of PPAR[gamma]-KO and wild-type mice post-instillation with MWCNT and MWCNT+ESAT-6, and flow cytometric analyses revealed that CD4+ T cells were significantly elevated in PPAR[gamma]KO mice receiving MWCNT+ESAT-6. These findings suggest that instillation of PPAR[gamma]-KO mice with MWCNT+ESAT-6 elicits an exacerbated granulomatous and T lymphocyte mediated response.;

504 a| Includes bibliographical references.;

650 2 a| Sarcoidosis, Pulmonary.=| ^A945285;

650 2 a| T-Lymphocytes.=| ^A919189;

650 2 a| PPAR gamma.=| ^A1032977;

650 2 a| Disease Models, Animal.=| ^A918974;

650 2 a| Lymphocytes.=| ^A919187;

650 2 a| Mice.=| ^A921375;

650 2 a| Transcription Factors.=| ^A928861;

653 a| Granuloma;

653 a| Mycobacterial antigens;

653 a| Carbon nanotubes;

700 1 a| Mohan, Arjun,e| degree supervisor.=| ^A1471861;

710 2 a| Brody School of Medicine.b| Office of Research and Graduate Studies.b| Biomedical Sciences.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine thesis.=| ^A964744;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/7481;

949 o| wjh;

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999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5168863-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 8/27/2019x| ETDz| HERESOURCE;

Peroxisome proliferator-activated receptor gamma deficiency promotes a T lymphocyte response in a murine model of chronic pulmonary sarcoidosis / by Victoria L. Sanderford.

Author/creator	Sanderford, Victoria L. author.
Other author	Mohan, Arjun, degree supervisor.
Other author	Brody School of Medicine. Office of Research and Graduate Studies. Biomedical Sciences.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2019.
Description	91 pages : color illustrations.
Supplemental Content	Access via ScholarShip
Subjects	Sarcoidosis, Pulmonary. T-Lymphocytes. PPAR gamma. Disease Models, Animal. Lymphocytes. Mice. Transcription Factors.

Series	ECU Brody School of Medicine thesis ECU Brody School of Medicine thesis. ^A964744
Summary	Sarcoidosis is a chronic granulomatous disease of unknown etiology. Previous studies from our lab have shown a deficiency of the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPAR[gamma]) in the alveolar macrophages of sarcoidosis patients. We established a murine model of granuloma formation by instillation with multiwall carbon nanotubes (MWCNT), and the expression of PPAR[gamma] was also decreased in MWCNT instilled mice. There is evidence linking lymphocyte reactivity to mycobacterial antigens in sarcoidosis, so we hypothesized that addition of mycobacterial peptide early secretory antigenic target 6 (ESAT-6) to MWCNT might exacerbate the murine T effector cell response. MWCNT with or without ESAT-6 peptide 14 were instilled into macrophage-specific PPAR[gamma]-KO or wild-type mice. Controls received vehicle or ESAT-6 alone. Bronchoalveolar lavage (BAL) fluid was collected for analysis via qPCR, and lymph nodes were collected for histology, qPCR, in vitro studies, or flow cytometric analysis. PPAR[gamma]-KO mice receiving MWCNT+ESAT-6 displayed markedly increased granuloma formation and exhibited mediastinal lymphadenopathy. Additionally, PPAR[gamma]-KO mice treated with MWCNT+ESAT-6 exhibited exacerbated fibrotic severity at 20- and 60- days post-instillation. Similarly, lymphocyte frequency was elevated in the BAL of PPAR[gamma]-KO mice compared to controls at 20- and 60-days post-instillation with MWCNT+ESAT-6. Further, TH17 associated transcription factor ROR[gamma]t and immune regulatory marker PD1 were elevated in PPAR[gamma]-KO mice treated with MWCNT+ESAT-6 compared to sham mice at both time points, with elevation of multiple other TH17 associated genes at 60 days post instillation. Carbon nanotubes were observed in the mediastinal lymph nodes of PPAR[gamma]-KO and wild-type mice post-instillation with MWCNT and MWCNT+ESAT-6, and flow cytometric analyses revealed that CD4+ T cells were significantly elevated in PPAR[gamma]KO mice receiving MWCNT+ESAT-6. These findings suggest that instillation of PPAR[gamma]-KO mice with MWCNT+ESAT-6 elicits an exacerbated granulomatous and T lymphocyte mediated response.
General note	Presented to the faculty of the MS Program in Biomedical Sciences
General note	Advisor: Arjun Mohan
General note	Title from PDF t.p. (viewed November 14, 2019).
Dissertation note	M.S. East Carolina University 2019.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Peroxisome proliferator-activated receptor gamma deficiency promotes a T lymphocyte response in a murine model of chronic pulmonary sarcoidosis / by Victoria L. Sanderford.

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