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035 a| (Sirsi) o1257305145;

035 a| (OCoLC)1257305145;

049 a| EREE;

100 1 a| Psaltis, Christine E.,e| author.?| UNAUTHORIZED;

245 10 a| Prohibitin :b| a novel regulator of inflammatory cell dynamics /c| by Christine E. Psaltis.;

246 3 a| Prohibitin a novel regulator of inflammatory cell dynamics;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2020.;

300 a| 114 pages :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 1.54 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

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

502 b| Ph.D.c| East Carolina Universityd| 2020.;

500 a| Presented to the faculty of the Department of Pharmacology and Toxicology;

500 a| Advisor: Kymberly Gowdy;

500 a| Title from PDF t.p. (viewed September 1, 2021).;

520 3 a| Inflammation is a complex mechanism primarily driven by the immune system to eradicate pathogens/foreign substances and restore tissue homeostasis. Despite the beneficial effects that inflammation employs, signaling can often become dysregulated leading to uncontrolled systemic inflammation and irreversible host tissue damage. Therefore, regulating the cellular and physiological mechanisms of inflammation constitutes a viable avenue of research to mitigate inflammatory disease progression. Herein, we evaluated prohibitins (PHB1 and PHB2), pleiotropic homologous proteins with known anti-inflammatory and antioxidant capabilities, in the context of systemic inflammation as well as macrophage-specific inflammatory signaling. Using two in vivo models of systemic inflammation, we found that PHB1 levels were increased in serum, suggesting a potential signaling role for PHB. Moreover, recombinant PHB1 treatment mitigated systemic inflammation and tissue/organ injury and modulated the phenotype of circulating immune cells. When investigating the role of PHB specifically in monocytes/macrophages, we found that PHB not only increased populations of pro-inflammatory monocytes in vivo but also regulated vital macrophage inflammatory signaling (as shown in vitro). We determined that PHB is a scaffold protein important for macrophage lipid raft formation and subsequent receptor trafficking. PHB modulation of macrophages influenced cell surface display of lipid-raft-dependent receptors and downstream inflammatory signaling cascades. To our knowledge, these are the first data to reveal PHB's pro-inflammatory effects in macrophages and its mechanistic operation of lipid-raft-dependent signal transduction in macrophages. In this report, we provide insight into the diverse yet complementary roles of PHB in regulating various aspects of immune-driven inflammatory processes.;

504 a| Includes bibliographical references.;

650 2 a| Prohibitin.?| UNAUTHORIZED;

650 2 a| Repressor Proteins.=| ^A1203871;

650 2 a| Durable Medical Equipment.=| ^A1001394;

653 a| inflammation;

653 a| sepsis;

653 a| macrophage;

653 a| lipid raft;

700 1 a| Gowdy, Kymberly,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Pharmacology and Toxicology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/9101;

949 o| wjh;

994 a| C0b| ERE;

096 a| QU 34;

596 a| 1 4;

998 a| 5636900;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5636900-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 6/22/2021x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5636900-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 6/22/2021x| ETDz| HERESOURCE;

Prohibitin : a novel regulator of inflammatory cell dynamics / by Christine E. Psaltis.

Author/creator	Psaltis, Christine E. author.
Other author	Gowdy, Kymberly, degree supervisor.
Other author	East Carolina University. Department of Pharmacology and Toxicology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2020.
Description	114 pages : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Prohibitin. Repressor Proteins. Durable Medical Equipment.

Variant title	Prohibitin a novel regulator of inflammatory cell dynamics
Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Inflammation is a complex mechanism primarily driven by the immune system to eradicate pathogens/foreign substances and restore tissue homeostasis. Despite the beneficial effects that inflammation employs, signaling can often become dysregulated leading to uncontrolled systemic inflammation and irreversible host tissue damage. Therefore, regulating the cellular and physiological mechanisms of inflammation constitutes a viable avenue of research to mitigate inflammatory disease progression. Herein, we evaluated prohibitins (PHB1 and PHB2), pleiotropic homologous proteins with known anti-inflammatory and antioxidant capabilities, in the context of systemic inflammation as well as macrophage-specific inflammatory signaling. Using two in vivo models of systemic inflammation, we found that PHB1 levels were increased in serum, suggesting a potential signaling role for PHB. Moreover, recombinant PHB1 treatment mitigated systemic inflammation and tissue/organ injury and modulated the phenotype of circulating immune cells. When investigating the role of PHB specifically in monocytes/macrophages, we found that PHB not only increased populations of pro-inflammatory monocytes in vivo but also regulated vital macrophage inflammatory signaling (as shown in vitro). We determined that PHB is a scaffold protein important for macrophage lipid raft formation and subsequent receptor trafficking. PHB modulation of macrophages influenced cell surface display of lipid-raft-dependent receptors and downstream inflammatory signaling cascades. To our knowledge, these are the first data to reveal PHB's pro-inflammatory effects in macrophages and its mechanistic operation of lipid-raft-dependent signal transduction in macrophages. In this report, we provide insight into the diverse yet complementary roles of PHB in regulating various aspects of immune-driven inflammatory processes.
General note	Presented to the faculty of the Department of Pharmacology and Toxicology
General note	Advisor: Kymberly Gowdy
General note	Title from PDF t.p. (viewed September 1, 2021).
Dissertation note	Ph.D. East Carolina University 2020.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Prohibitin : a novel regulator of inflammatory cell dynamics / by Christine E. Psaltis.

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