Open Access. Powered by Scholars. Published by Universities.®

Cell Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 10 of 10

Full-Text Articles in Cell Biology

Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long Dec 2014

Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long

Theses and Dissertations

Tularemia is a potentially fatally illness caused by the facultative intracellular Gram-negative bacterium Francisella tularensis. Virulent strains of F. tularensis can cause a fatal disease after inhalation of a few as ten organisms. Due to the highly pathogenic features of Francisella, it has been designated as a Tier 1 select agent, meaning that its possession and handling is highly restricted. Macrophages are phagocytes that play a central role in the innate immune response to infection that can be used by certain pathogens, including Francisella, as a niche for bacterial replication and dissemination during infection. After infection of macrophages Francisella escapes ...


Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao Sep 2014

Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao

UMass Center for Clinical and Translational Science Supported Publications

Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed ...


Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock Aug 2014

Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock

Open Access Articles

When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been ...


Neutrophil Priming And Host Inflammation: The Roles Of Nox2 And Toll-Like Receptors, Laura Christine Whitmore May 2014

Neutrophil Priming And Host Inflammation: The Roles Of Nox2 And Toll-Like Receptors, Laura Christine Whitmore

Theses and Dissertations

Neutrophils, essential innate immune cells, recognize danger signals through receptors on their surface. Upon receptor ligation, neutrophils may undergo priming, a process involving limited reactive oxygen species (ROS) generation and partial degranulation. Priming facilitates neutrophil migration and prepares the cell for an enhanced response to a secondary stimulus, including a spike in ROS generation by NADPH oxidase 2 (NOX2). It is well established that NOX2-derived oxidants are involved in pathogen killing and that off-target effects can cause host tissue damage; however, several lines of recent evidence also support an anti-inflammatory function for NOX2 oxidants. First, patients with chronic granulomatous disease ...


Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz Feb 2014

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are ...


Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro Jan 2014

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair ...


The Long Noncoding Rna Thril Regulates Tnfalpha Expression Through Its Interaction With Hnrnpl, Zhonghan Li, Ti-Chun Chao, Kung-Yen Chang, Nianwei Lin, Veena S. Patil, Chisato Shimizu, Steven R. Head, Jane C. Burns, Tariq M. Rana Jan 2014

The Long Noncoding Rna Thril Regulates Tnfalpha Expression Through Its Interaction With Hnrnpl, Zhonghan Li, Ti-Chun Chao, Kung-Yen Chang, Nianwei Lin, Veena S. Patil, Chisato Shimizu, Steven R. Head, Jane C. Burns, Tariq M. Rana

GSBS Student Publications

Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFalpha expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of ...


Role Of Pikfyve In Platelet Lysosomal Homeostasis, Sang Hee Min Jan 2014

Role Of Pikfyve In Platelet Lysosomal Homeostasis, Sang Hee Min

Publicly Accessible Penn Dissertations

PIKfyve is a lipid kinase that is essential for the synthesis of phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2], and for the regulation of membrane dynamics within the endolysosomal system in mammals. Depletion of intracellular pools of PtdIns(3,5)P2 in humans and in mice is associated with neurodegeneration and early lethality. However, the biological role of PtdIns(3,5)P2 in non-neural tissues is not well understood. Platelets are hematopoietic cells that function in a variety of physiological responses. Essential to many of these functions is the activation-dependent release of effectors from distinct storage granules - alpha granules, dense granules ...


The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence Jan 2014

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells ...


Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay Jan 2014

Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay

Publicly Accessible Penn Dissertations

Hypoxia-inducible factors (HIFs) mediate adaptation to low O2, or hypoxia, are important at every stage of tumor initiation, and impact the progression of a variety of diseases, including colorectal cancer. This body of work investigates the role of hypoxia and HIF-mediated signaling in both tumor cells and macrophages across the natural history of inflammation-induced cancers. First, the effect of HIF inhibition in tumor parenchyma and stroma in extant colitis-associated colon carcinomas (CAC) is investigated using acriflavine (ACF), a naturally occurring compound known to repress HIF transcriptional activity. Pharmacologic HIF inhibition represents a novel therapeutic strategy for cancer treatment and data ...