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2014

Inflammation

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Role Of Mycoplasma Gallisepticum And Host Airway Epithelial Cell Interaction In Inflammation, Sanjukta Majumder Dec 2014

Role Of Mycoplasma Gallisepticum And Host Airway Epithelial Cell Interaction In Inflammation, Sanjukta Majumder

Doctoral Dissertations

Mycoplasma gallisepticum infection in chickens is associated with severe inflammation of the trachea, air sacs and lungs. M. gallisepticum cytadheres to the tracheal epithelium and mediates infiltration of macrophages, heterophils and lymphocytes to the tracheal submucosa but the molecular mechanisms underpinning the severe inflammatory response is not well understood. This research focuses on identifying how M. galisepticum and chicken tracheal epithelial cell (TEC) interaction might contribute to this response. The first study identified that M. gallisepticum lipid associated membrane proteins (LAMP) from both virulent and non-virulent strains were able to up-regulate several inflammatory genes from tracheal epithelial cells both in …


Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, And Inflammation, Chang Kim, Jeongho Park, Myunghoo Kim Dec 2014

Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, And Inflammation, Chang Kim, Jeongho Park, Myunghoo Kim

Department of Comparative Pathobiology Faculty Publications

T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We …


Taking The Perspective That A Depressive State Reflects Inflammation: Implications For The Use Of Antidepressants, Jill Littrell Dec 2014

Taking The Perspective That A Depressive State Reflects Inflammation: Implications For The Use Of Antidepressants, Jill Littrell

jill l littrell Dr.

This paper reviews both the evidence that supports the characterization of depression as an inflammatory disorder and the different biochemical mechanisms that have been postulated for the connection between inflammation and depression. This association offers credible explanation for the short term efficacy of antidepressants, which have short term anti-inflammatory effects. Evidence for those anti-inflammatory effects is discussed. Evidence of the contrary long-term effects of antidepressants, which increase rather than decrease inflammation, is also reviewed. It is argued that this increase in inflammation would predict an increase in chronicity among depressed patients that have been treated with antidepressants drugs, which has …


Diversity, Genetics, And Health Benefits Of Sorghum Grain, Davina Rhodes Dec 2014

Diversity, Genetics, And Health Benefits Of Sorghum Grain, Davina Rhodes

Theses and Dissertations

Staple cereal crops provide the majority of nutrients to the world's population, and thus, can significantly impact human nutrition and health. Phenotypic and genetic diversity within a crop can be useful for biofortification and crop improvement, but quantitative phenotyping is needed to identify varieties with high or low concentrations of a nutrient of interest, and to identify alleles responsible for quantitative trait variation of the nutrient. Sorghum [Sorghum bicolor (L.) Moench] is a diverse and widely adapted cereal crop that provides food for more than 500 million people in sub-Saharan Africa and Asia, and is becoming increasingly popular in specialty …


Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan Dec 2014

Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan

Theses and Dissertations

The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. Tumors associated macrophages drive the pro-inflammatory response in the tumor micro-environment and are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. In chapter 1, we examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in …


Heat-Killed Probiotic Bacteria Differentially Regulate Colonic Epithelial Cell Production Of Human Β-Defensin-2: Dependence On Inflammatory Cytokines., N. Habil, W. Abate, J. Beal, A. D. Foey Dec 2014

Heat-Killed Probiotic Bacteria Differentially Regulate Colonic Epithelial Cell Production Of Human Β-Defensin-2: Dependence On Inflammatory Cytokines., N. Habil, W. Abate, J. Beal, A. D. Foey

School of Biomedical Sciences

The inducible antimicrobial peptide human β-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) …


Associations Between Vitamin D Status, Adiposity, And Inflammatory Biomarkers In Young Women (18 – 30 Years), Adolphina Addo-Lartey Nov 2014

Associations Between Vitamin D Status, Adiposity, And Inflammatory Biomarkers In Young Women (18 – 30 Years), Adolphina Addo-Lartey

Doctoral Dissertations

We conducted a cross-sectional analysis among 270 (18- to 30-year old) female participants in the UMass Amherst Vitamin D Status Study (n = 270) to assess the extent to which dietary intakes of calcium and vitamin D are associated with obesity markers. We also evaluated the association between serum 25-OHD concentrations and both adiposity and inflammatory biomarkers. Study participants were mostly Caucasians (84.5%) with normal BMI, although about half of women had high adiposity (total body fat ‘TBF’≥ 32%). Women reporting adequate intakes of calcium (≥ 1000 mg/day) but low intakes of vitamin D (< 600 IU/day) were more than twice as likely to have a high percentage of TBF compared to women with adequate intakes of both calcium and vitamin D. In addition, women with lower calcium intake from supplements were twice as likely to have a waist circumference ≥ 80 cm (OR = 2.04; 95% CI: 1.04 – 3.99) compared to women in the highest tertile of calcium intake. The magnitude of this association is important since among young women 18-30 years old, a waist circumference greater than 80 cm indicates central obesity and suggests increased visceral adiposity, which contributes to hyperlipidemia and other obesity-related chronic conditions. Among all women, total vitamin D, food vitamin D, and supplemental vitamin D intake were not associated with serum 25-OHD concentration (P > 0.05). However, among supplement …


Factors Of Inflammation In Haitian Americans And African Americans With And Without Type 2 Diabetes, Janet Antwi Nov 2014

Factors Of Inflammation In Haitian Americans And African Americans With And Without Type 2 Diabetes, Janet Antwi

FIU Electronic Theses and Dissertations

Chronic low-grade inflammation has been implicated in the processes leading to the development of type 2 diabetes (T2D) and its progression. Non-Hispanic Blacks bear a disproportionate burden of T2D and are highly susceptible to inflammation. This cross-sectional study assessed and compared the serum levels of established adipocytokines; interleukin-6 (IL-6), C-reactive protein (CRP), leptin, and novel adipocytokines; chemerin and omentin in Haitian and African Americans with and without T2D. The relationships of these adipocytokines with metabolic syndrome (MetS), anthropometric and HOMA2 measures by ethnicity and diabetes status were also assessed. Serum levels of IL-6, CRP, leptin, chemerin and omentin were determined …


Synergistic Effect Of Pro-Inflammatory Tnfα And Il-17 In Periostin Mediated Collagen Deposition: Potential Role In Liver Fibrosis, Suneetha Amara, Karina Lopez, Babak Banan, Sade-Kemi Brown, Margaret Whalen, Elbert L. Myles, Michael T. Ivy, Terrance Johnson, Kevin L. Schey, Venkataswarup Tiriveedhi Nov 2014

Synergistic Effect Of Pro-Inflammatory Tnfα And Il-17 In Periostin Mediated Collagen Deposition: Potential Role In Liver Fibrosis, Suneetha Amara, Karina Lopez, Babak Banan, Sade-Kemi Brown, Margaret Whalen, Elbert L. Myles, Michael T. Ivy, Terrance Johnson, Kevin L. Schey, Venkataswarup Tiriveedhi

Biology Faculty Research

Background

The pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-17, have been implicated in the pathogenesis of liver fibrosis. In this study, we investigated the role of TNFα and IL-17 toward induction of profibrotic factor, periostin.

Methods

HepG2 cells were cultured and treated with inflammatory cytokines, TNFα and IL-17. Computational promoter sequence analysis of the periostin promoter was performed to define the putative binding sites for transcription factors. Transcription factors were analyzed by Western blot and Chromatin Immunoprecipitation. Periostin and transcription factor expression analysis was performed by RT-PCR, Western blot, and fluorescence microscopy. Type I collagen expression from fibroblast …


Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero Nov 2014

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …


Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley Nov 2014

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …


Caveolin-1 Deletion Exacerbates Cardiac Interstitial Fibrosis By Promoting M2 Macrophage Activation In Mice After Myocardial Infarction, Pooja Shivshankar, Ganesh V. Halade, Cheresa Calhoun, Gladys P. Escobar, Ali J. Mehr, Fabio Jimenez, Cindy Martinez, Harshita Bhatnagar, Corey H. Mjaatvedt, Merry L. Lindsey, Claude Jourdan Le Saux Nov 2014

Caveolin-1 Deletion Exacerbates Cardiac Interstitial Fibrosis By Promoting M2 Macrophage Activation In Mice After Myocardial Infarction, Pooja Shivshankar, Ganesh V. Halade, Cheresa Calhoun, Gladys P. Escobar, Ali J. Mehr, Fabio Jimenez, Cindy Martinez, Harshita Bhatnagar, Corey H. Mjaatvedt, Merry L. Lindsey, Claude Jourdan Le Saux

Internal Medicine Faculty Publications

Adverse remodeling following myocardial infarction (MI) leading to heart failure is driven by an imbalanced resolution of inflammation. The macrophage cell is an important control of post-MI inflammation, as macrophage subtypes secrete mediators to either promote inflammation and extend injury (M1 phenotype) or suppress inflammation and promote scar formation (M2 phenotype). We have previously shown that the absence of caveolin-1 (Cav1), a membrane scaffolding protein, is associated with adverse cardiac remodeling in mice, but the mechanisms responsible remain to be elucidated. We explore here the role of Cav1 in the activation of macrophages using wild type C57BL6/J (WT) and Cav1tm1Mls/J …


Pharmacologic Immunomodulation Of Macrophage Activation By Caffeine, Ryan Perry Steck Oct 2014

Pharmacologic Immunomodulation Of Macrophage Activation By Caffeine, Ryan Perry Steck

Theses and Dissertations

Caffeine is one of the most widely used neurostimulants in the world and there is considerable debate on its effect in immune cells. One of its main targets is proposed to be adenosine receptors which mediate an anti-inflammatory switch in activated immune cells while another target is phosphodiesterase where it acts as an inhibitor. In macrophages, caffeine has been shown to cause both pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. If the primary effect of caffeine on macrophages were to antagonize adenosine receptors we would expect cells exposed to caffeine to have a prolonged M1 response. However, we show that caffeine …


Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo Sep 2014

Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-alpha (TNFalpha), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1beta). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-kappaB (NF-kappaB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol-containing or isocaloric …


Myeloid Derived Hypoxia Inducible Factor 1-Alpha Is Required For Protection Against Pulmonary Aspergillus Fumigatus Infection, Kelly M. Shepardson, Anupam Jhingran, Alayna Caffrey, Joshua J. Obar, Benjamin T. Suratt, Brent L. Berwin, Tobias M. Hohl, Robert A. Cramer Sep 2014

Myeloid Derived Hypoxia Inducible Factor 1-Alpha Is Required For Protection Against Pulmonary Aspergillus Fumigatus Infection, Kelly M. Shepardson, Anupam Jhingran, Alayna Caffrey, Joshua J. Obar, Benjamin T. Suratt, Brent L. Berwin, Tobias M. Hohl, Robert A. Cramer

Dartmouth Scholarship

Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial …


Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston Sep 2014

Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston

Journal Articles: Ophthalmology

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual …


Calcineurin And Glial Signaling: Neuroinflammation And Beyond, Jennifer L. Furman, Christopher M. Norris Sep 2014

Calcineurin And Glial Signaling: Neuroinflammation And Beyond, Jennifer L. Furman, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca2+ dyshomeostasis, and amyloid production suggest that CN's influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, …


A Double-Blind Randomized Trial Of Fish Oil To Lower Triglycerides And Improve Cardiometabolic Risk In Adolescents., Samuel S. Gidding, Carol Prospero, Jobayer Hossain, Frances Zappalla, Prabhakaran Babu Balagopal, Bonita Falkner, Peter Kwiterovich Sep 2014

A Double-Blind Randomized Trial Of Fish Oil To Lower Triglycerides And Improve Cardiometabolic Risk In Adolescents., Samuel S. Gidding, Carol Prospero, Jobayer Hossain, Frances Zappalla, Prabhakaran Babu Balagopal, Bonita Falkner, Peter Kwiterovich

Department of Pediatrics Faculty Papers

OBJECTIVES: To determine the efficacy of 4 g/day fish oil to lower triglycerides and impact lipoprotein particles, inflammation, insulin resistance, coagulation, and thrombosis.

STUDY DESIGN: Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured.

RESULTS: Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean …


Regulation Of Fluid-Phase Uptake In Podocytes By Albumin-Associated Lipids, Jun-Jae Chung Sep 2014

Regulation Of Fluid-Phase Uptake In Podocytes By Albumin-Associated Lipids, Jun-Jae Chung

All Theses and Dissertations (ETDs)

I. Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. In nephrotic syndrome, a major breakdown of the kidney filtration barrier associated with proteinuria, hyperlipidemia, and edema, podocytes undergo changes in morphology and appear to internalize serum proteins. We postulated that fluid-phase uptake by podocytes might play a role in maintaining the integrity of the filtration barrier. Using fluid-phase tracers, we show that podocytes in vivo actively internalize fluid from the serum and that the rate of internalization is enhanced when the filtration barrier is disrupted. In vitro …


Micrornas In Als: Defining Cell-Type Specific Expression, Developing Methods To Modulate Micrornas In Vivo, And Identifying Novel Therapeutic Targets, Erica Danielle Koval Sep 2014

Micrornas In Als: Defining Cell-Type Specific Expression, Developing Methods To Modulate Micrornas In Vivo, And Identifying Novel Therapeutic Targets, Erica Danielle Koval

All Theses and Dissertations (ETDs)

Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neuromuscular disease with no adequate therapies. MicroRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS model SOD1G93A rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. Generation of mice that express a GFP-tagged miRNA processing protein behind cell-type specific promoters allowed for the identification of miRNA expression patterns …


Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa Aug 2014

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …


Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale Aug 2014

Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale

Theses and Dissertations

Cachexia is a multifactorial syndrome that manifests during the advanced stage of chronic diseases and is characterized by a progressive loss of body mass sustained by underlying inflammation. The ApcMin/+ mouse is an established model of cachexia that exhibits a gradual loss of body mass correlating with increasing tumor burden and plasma IL – 6 levels. Moreover it also mimics other secondary characteristics observed in cachectic patients like splenomegaly, elevated plasma endotoxin levels, gut barrier dysfunction, hypogonadism and an overall hypermetabolic state. Liver controls the energy metabolism in the body by regulating glucose and lipid metabolism, glycogen storage, filtration of …


The Effects Of Leucine And Dairy Products On Adipose Tissue Inflammation: The Role Of Adipocyte Derived Microvesicles, Benjamin Jones Curry Aug 2014

The Effects Of Leucine And Dairy Products On Adipose Tissue Inflammation: The Role Of Adipocyte Derived Microvesicles, Benjamin Jones Curry

Doctoral Dissertations

Obesity is characterized by chronic oxidative and inflammatory stress, and adipose tissue is a significant source of inflammatory cytokines. Previous studies demonstrated that dairy products (rich in calcium and leucine) can alleviate obesity-associated inflammatory stress through suppression of 1, 25-dihydroxycholecalciferol (calcitriol) with calcium and the high leucine content in dairy. We have also shown leucine treatment increases anti-inflammatory adiponectin expression and decreases pro-inflammatory cytokines TNF-a [alpha], MCP-1, and IL-6 expression in adipocytes. Therefore, we sought to determine if these alterations in inflammatory cytokine production could have a functional effect on the inflammatory process, specifically monocyte – endothelial cell adhesion as …


Eccentric Muscle Challenge Shows Osteopontin Polymorphism Modulation Of Muscle Damage., Whitney L. Barfield, Kitipong Uaesoontrachoon, Chung-Sheih Wu, Stephen Lin, Yue Chen, Paul C. Wang, Yasmine Kanaan, Vernon Bond, Eric P. Hoffman Aug 2014

Eccentric Muscle Challenge Shows Osteopontin Polymorphism Modulation Of Muscle Damage., Whitney L. Barfield, Kitipong Uaesoontrachoon, Chung-Sheih Wu, Stephen Lin, Yue Chen, Paul C. Wang, Yasmine Kanaan, Vernon Bond, Eric P. Hoffman

Genomics and Precision Medicine Faculty Publications

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitroreporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric …


Dissecting The Roles Of Trim24 In Regulation Of Hepatic Lipid Metabolism And Inflammation, Lindsey C. Minter Aug 2014

Dissecting The Roles Of Trim24 In Regulation Of Hepatic Lipid Metabolism And Inflammation, Lindsey C. Minter

Dissertations & Theses (Open Access)

DISSECTING THE ROLES OF TRIM24 IN REGULATION OF HEPATIC LIPID

METABOLISM AND INFLAMMATION

Lindsey Cauthen Minter, B.S., B.A.

Advisory Professor: Michelle C. Barton, Ph.D.

In this dissertation, I report the characterization of a new mouse model that recapitulates development of hepatocellular carcinoma (HCC) following spontaneous hepatic lipid accumulation, inflammation, and damage of liver tissue, due to complete loss of Trim24 expression. In human HCC and other cancers, TRIM24 expression is aberrantly high, while deletion of TRIM24 in the mouse has been shown to act as a liver specific tumor suppressor. The hypothesis tested here was that TRIM24, the E3 ubiquitin …


The Effect Of A Community-Based Exercise Program On Inflammation, Metabolic Risk, And Fitness Levels Among Persons Living With Hiv/Aids, Stacy E. Cutrono Jul 2014

The Effect Of A Community-Based Exercise Program On Inflammation, Metabolic Risk, And Fitness Levels Among Persons Living With Hiv/Aids, Stacy E. Cutrono

Open Access Dissertations

The Human Immunodeficiency Virus (HIV) pandemic remains a top national health priority. Chronic inflammation may be a critical component in the disease course of HIV as C-reactive protein (CRP) is elevated and associated with increased mortality. This study examined the effect of three months of combined aerobic and resistance exercise training among a diverse cohort of HIV-infected men and women. The fixed effect of time for CRP was found to be non-significant (F[1,57.3]=1.7, p=0.19). There was a significant fixed effect for time for upper body (F[1,51.6]=18.1, p<0.05) and lower body strength (F[1,48.0]=15.7, p<0.05) and significant declines in diastolic blood pressure (p=0.002) and waist circumference (p=0.027). Though levels of CRP were not impacted after three months training, participants demonstrated a significant increase in muscular strength as well as beneficial changes in metabolic risk factors. Future studies should focus on determining the optimal exercise intervention length and mode to reduce inflammation.


Transition From An M1 To A Mixed Neuroinflammatory Phenotype Increases Amyloid Deposition In App/Ps1 Transgenic Mice, Erica M. Weekman, Tiffany L. Sudduth, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Holly M. Brothers, Kaitlyn Braun, Abigail Greenstein, Donna M. Wilcock Jul 2014

Transition From An M1 To A Mixed Neuroinflammatory Phenotype Increases Amyloid Deposition In App/Ps1 Transgenic Mice, Erica M. Weekman, Tiffany L. Sudduth, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Holly M. Brothers, Kaitlyn Braun, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer's disease, yet the impact of these phenotypes on amyloid-beta (Aβ) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces Aβ, but long-term studies have not been performed that track the neuroinflammatory phenotype.

METHODS: Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a bilateral intracranial injection of adeno-associated viral (AAV) vectors expressing IFNγ or green fluorescent protein in the frontal cortex and hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFNγ protein levels and …


Association Of Trauma Exposure With Proinflammatory Activity: A Transdiagnostic Meta-Analysis., M Tursich, R W J Neufeld, P A Frewen, S Harricharan, J L Kibler, S G Rhind, R A Lanius Jul 2014

Association Of Trauma Exposure With Proinflammatory Activity: A Transdiagnostic Meta-Analysis., M Tursich, R W J Neufeld, P A Frewen, S Harricharan, J L Kibler, S G Rhind, R A Lanius

Faculty Articles

Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one's risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. …


Osteopontin: A Novel Regulator At The Cross Roads Of Inflammation, Obesity And Diabetes, Florian Kahles, Hannes M. Findeisen, Dennis Bruemmer Jul 2014

Osteopontin: A Novel Regulator At The Cross Roads Of Inflammation, Obesity And Diabetes, Florian Kahles, Hannes M. Findeisen, Dennis Bruemmer

Gill Heart & Vascular Institute Faculty Publications

Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and …


The Interrelationship Of Brca1 185delag, Interleukin-1Β, And Ovarian Oncogenesis, Kamisha Woolery Jun 2014

The Interrelationship Of Brca1 185delag, Interleukin-1Β, And Ovarian Oncogenesis, Kamisha Woolery

USF Tampa Graduate Theses and Dissertations

While the etiology of ovarian cancer (OC) is not completely understood, evidence suggests that chronic inflammation may promote malignant transformation. However, familial history remains the strongest risk factor for developing OC and is associated with germline BRCA1 mutations, such as the 185delAG mutation. Normal human ovarian surface epithelial cells expressing the 185delAG mutant, BRAT, exhibit molecular and pathological changes that may contribute to OC oncogenesis. In the current study, I sought to determine whether BRAT could promote an inflammatory phenotype by investigating BRAT's impact on the expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Using a culture model system of normal …