자료유형  

 학위논문

Control Number  

0016934454

International Standard Book Number  

9798380481373

Dewey Decimal Classification Number  

600

Main Entry-Personal Name  

Shehabeldin, Mostafa Salah.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pittsburgh., 2021

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2021

Physical Description  

1 online resource(139 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-04, Section: B.

General Note  

Advisor: Sfeir, Charles.

Dissertation Note  

Thesis (Ph.D.)--University of Pittsburgh, 2021.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Periodontal disease (PD) is a chronic inflammatory disease characterized by progressive destruction of tooth supporting structures and microbial dysbiosis. The destructive inflammatory process underlying PD is mediated by components of both the innate and acquired immune systems including immune cells, cytokines, chemokines and lipid mediators. Macrophages and Thelper 17 (Th17) cells are key cellular mediators of the innate and acquired host responses in the periodontal environment, respectively. In many tissues including the periodontium, macrophages are the prototypic phagocytes of the innate immune response. These plastic cells can assume distinct phenotypic subsets to perform a wide array of functions ranging from host defense against invading pathogens to clearance of dead cells and promotion of tissue repair. Similarly, periodontal Th17 cells can exhibit both homeostatic and pathogenic subsets. Homeostatic Th17 cells are essential for immune surveillance and host defense by regulating neutrophils expansion and recruitment at oral barrier sites. Conversely, pathogenic Th17 cells arise in response to oral microbial challenge and drive inflammatory damage in PD via overproduction of their major cytokine IL-17A. In this study, we tested the therapeutic efficacy of modulating macrophages response or IL-17A activity in PD using two polymer based sustained delivery systems. To target macrophages, the chemokine CCL2 was encapsulated in PLGA microspheres and locally delivered at different stages of murine PD severity followed by analysis of bone levels, gene expression profile, osteoclastic activity, periodontal ligament organization and periodontal microbial load and composition. Using Sc-RNA sequencing technology, we also assessed murine periodontal macrophages gene expression profile and characterized their phenotypic subsets. We also tested the protective effect of local sustained delivery of IL-17A antibodies in murine periodontitis by assessing the changes in bone levels, osteoclastic activity and inflammatory markers. The overall aim of this study was to highlight the clinical translation potential of targeting cellular and noncellular components of the innate and acquired immune response to treat PD.

Subject Added Entry-Topical Term  

Infections.

Subject Added Entry-Topical Term  

Pathogens.

Subject Added Entry-Topical Term  

Chemokines.

Subject Added Entry-Topical Term  

Biofilms.

Subject Added Entry-Topical Term  

Periodontium.

Subject Added Entry-Topical Term  

Cytokines.

Subject Added Entry-Topical Term  

Inflammation.

Subject Added Entry-Topical Term  

Disease prevention.

Subject Added Entry-Topical Term  

Medical imaging.

Subject Added Entry-Topical Term  

Debridement.

Subject Added Entry-Topical Term  

Ligaments.

Subject Added Entry-Topical Term  

Homeostasis.

Subject Added Entry-Topical Term  

Fibroblasts.

Subject Added Entry-Topical Term  

Collagen.

Subject Added Entry-Topical Term  

Connective tissue.

Subject Added Entry-Topical Term  

Microbiota.

Subject Added Entry-Topical Term  

Gum disease.

Subject Added Entry-Topical Term  

Three dimensional imaging.

Subject Added Entry-Topical Term  

Statistical significance.

Subject Added Entry-Topical Term  

Pathogenesis.

Subject Added Entry-Topical Term  

Enzymes.

Subject Added Entry-Topical Term  

Dental plaque.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Dentistry.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Pathology.

Subject Added Entry-Topical Term  

Physiology.

Subject Added Entry-Topical Term  

Surgery.

Added Entry-Corporate Name  

University of Pittsburgh.

Host Item Entry  

Dissertations Abstracts International. 85-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643325