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Characterization of Adipokine-Induced Responses for Inflammation and Leukocyte Interaction in Endothelial Cells

Singh, Manindra
http://orcid.org/0000-0003-0585-5502
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou150169740307715

Abstract Details

2017, Doctor of Philosophy (PhD), Ohio University, Biological Sciences (Arts and Sciences).
Without a doubt, the epidemic of obesity is one of the most serious health problems that affect millions of people worldwide and increases the risk of premature death. Studies indicate that chronic, low-grade inflammation is a major contributor of the obesity-associated pathogenesis, and therapeutic measures that target this process have been envisioned to be promising anti-obesity therapies. Adipokines - biologically active molecules secreted from adipose tissue - have been described as potential candidates for therapy given their capability to regulate numerous physiological responses, both at local and systemic levels. However, the mechanism by which adipokines regulate inflammatory processes, specifically in the vascular compartment of adipose tissue, is poorly understood. With a goal to provide evidence for their therapeutic value as well as to understand the mechanism by which adipokines regulate intercellular cross-talk between various signaling pathways, herewith we characterize in detail the regulatory role of an adipokine visfatin for inflammatory activation, leukocytosis (recruitment of leukocytes), and morphogenic responses in endothelial cells. It is hypothesized that visfatin treatment can activate endothelial cells to upregulate the secretion of chemokines and expression of inflammatory markers resulting in an enhanced leukocyte interaction. Consistently, we report that visfatin-treated endothelial cells exhibit an increased pro-inflammatory expression profile, enhanced chemokine secretion, and a pronounced capacity for leukocyte migration and attachment. We also evaluated the angiogenic capability of visfatin and report visfatin-mediated upregulation of multiple angiogenesis-associated genes and endothelial cells capillary-like tube formation in vitro. Furthermore, we report that visfatin-stimulated pro-inflammatory expression and chemokine secretion is predominantly mediated by the components of MAP kinase and NFkB signaling pathways. Finally, we show that pharmacological inhibition of visfatin can suppress the secretion of inflammatory chemokines by human endothelial cells. Thus, this work provides a detailed characterization of visfatin mediated responses that lead to inflammation in endothelial cells and provide further evidence for its potential role as a therapeutic target to reduce disease progression. Future in vivo studies are required to further delineate the physiological effect of adipokines for their regulation of metabolic and inflammatory functions. Towards this, we provide a qualitative profile for adipokine-responsive cytokine secretion as preliminary data that, hopefully, will be extended to the murine system.
Fabian Benencia, Ph.D. (Advisor)
John Kopchick, Ph.D. (Committee Member)
Darlene Berryman, Ph.D. (Committee Member)
Robert Colvin, Ph.D. (Committee Member)
Ramiro Malgor, MD (Committee Member)
205 p.
Biomedical Research; Health; Immunology; Molecular Biology
Inflammation; Adipokines; Endothelial Cells; Cytokines; Leukocytes; Obesity; Signal Transduction; Chemokines; Angiogenesis; Visfatin; Metabolic Disease; Vaspin; Leptin; Cancer; Inhibitors

Recommended Citations

Citations

  • Singh, M. (2017). Characterization of Adipokine-Induced Responses for Inflammation and Leukocyte Interaction in Endothelial Cells [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou150169740307715

    APA Style (7th edition)

  • Singh, Manindra. Characterization of Adipokine-Induced Responses for Inflammation and Leukocyte Interaction in Endothelial Cells. 2017. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou150169740307715.

    MLA Style (8th edition)

  • Singh, Manindra. "Characterization of Adipokine-Induced Responses for Inflammation and Leukocyte Interaction in Endothelial Cells." Doctoral dissertation, Ohio University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou150169740307715

    Chicago Manual of Style (17th edition)

ohiou150169740307715
267
© 2017, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.