Physiology Commons^™

Serum Amyloid A Impairs The Antiinflammatory Properties Of Hdl, Chang Yeop Han, Chongren Tang, Myriam E. Guevara, Hao Wei, Tomasz Wietecha, Baohai Shao, Savitha Subramanian, Mohamed Omer, Shari Wang, Kevin D. O'Brien, Santica M. Marcovina, Thomas N. Wight, Tomas Vaisar, Maria C. De Beer, Frederick C. De Beer, William R. Osborne, Keith B. Elkon, Alan Chait

Physiology Faculty Publications

HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO₃ fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO₃-injected mice lacking Saa1.1 …

Rnd3 As A Novel Target To Ameliorate Microvascular Leakage, Jerome W. Breslin, Dayle A. Daines, Travis M. Doggett, Kristine H. Kurtz, Flavia M. Souza-Smith, Xun E. Zhang, Mack H. Wu, Sarah Y. Yuan

Biological Sciences Faculty Publications

Background -Microvascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.

Methods and Results-Using immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate-albumin and transendothelial electrical resistance of human umbilical vein …

Ppap2b Expression Limits Lesion Formation In Murine Models Of Atherosclerosis, Paul A. Mueller

Theses and Dissertations--Physiology

Coronary artery disease (CAD) is the leading cause of death in both men and women worldwide and is defined as a narrowing of the coronary arteries due to accumulation of atherosclerotic plaques. Genome-wide association studies have identified risk loci within the gene PPAP2B that confers increased risk of developing CAD. Evidence suggests these aforementioned SNPs are regulating PPAP2B expression in a cis-manner through the interruption of transcription factor binding sites. PPAP2B encodes the lipid phosphate phosphatase 3 enzyme that plays a key role in degrading bioactive lysophosphatidic acid (LPA). LPA has a plethora of effects on vascular tissue and is …

Macrophage Migration Inhibitory Factor Mediates Par-Induced Bladder Pain., Dimitrios E. Kouzoukas, Katherine L. Meyer-Siegler, Fei Ma, Karin N. Westlund, David E. Hunt, Pedro L. Vera

Physiology Faculty Publications

INTRODUCTION: Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is constitutively expressed in urothelial cells that also express protease-activated receptors (PAR). Urothelial PAR1 receptors were shown to mediate bladder inflammation. We showed that PAR1 and PAR4 activator, thrombin, also mediates urothelial MIF release. We hypothesized that stimulation of urothelial PAR1 or PAR4 receptors elicits release of urothelial MIF that acts on MIF receptors in the urothelium to mediate bladder inflammation and pain. Thus, we examined the effect of activation of specific bladder PAR receptors on MIF release, bladder pain, micturition and histological changes.

METHODS: MIF release was measured …

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …

Determining The Role Of Il-4 Induced Neuroinflammation In Microglial Activity And Amyloid-Ss Using Bv2 Microglial Cells And App/Ps1 Transgenic Mice, Clare H. Latta, Tiffany L. Sudduth, Erica M. Weekman, Holly M. Brothers, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Floracita Gonzalez-Oregon, Kaitlyn Braun, Donna M. Wilcock

Physiology Faculty Publications

Background

Microglia are considered the resident immune cells of the central nervous system (CNS). In response to harmful stimuli, an inflammatory reaction ensues in which microglia are activated in a sequenced spectrum of pro- and antiinflammatory phenotypes that are akin to the well-characterized polarization states of peripheral macrophages. A “classically” activated M1 phenotype is known to eradicate toxicity. The transition to an “alternatively” activated M2 phenotype encompasses neuroprotection and repair. In recent years, inflammation has been considered an accompanying pathology in response to the accumulation of extracellular amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to drive an M2a-biased …

Acute Pro-Inflammatory Immune Response Following Different Resistance Exercise Protocols In Trained Men, Adam Wells

Electronic Theses and Dissertations

The successful regeneration of muscle tissue is dependent upon the infiltration of phagocytic CD14++CD16- monocytes that support the proliferation and differentiation of myogenic precursor cells. Physiologically, the magnitude of the cellular response following resistance exercise is dictated by the level of receptor expression on the plasma membrane of the monocyte, as well as the secretion of their cognate ligands from tissue resident cells. However, it remains unclear whether the innate pro-inflammatory immune response varies with different resistance training protocols, and how it may impact recovery and the muscle remodeling process. Therefore, the purpose of this investigation was to examine temporal …

Increased Circulatory Lipopolysaccharide From A High Fat Diet Aggravates Inflammation And Exacerbates Renal Failure, Samuel Righi

Theses and Dissertations

Kidney failure is frequently associated with the risk factors linked to metabolic syndrome. Lipopolysaccharide (LPS) is a potent inflammatory molecule, which has increased absorption from the gut into blood circulation following a high fat and high-energy diet. We hypothesized that LPS from a high fat diet can amplify inflammation, thereby exacerbating chronic kidney disease and associated disorders. We have found that adding a high fat diet to renal insufficient mice significantly progressed their kidney disease as well as associated disorders, compared to both a high fat diet and renal insufficiency alone. Additionally, we were able to demonstrate in vitro that …

Voluntary Exercise Reduces Alzheimer’S-Like Pathology After Inflammation In Mice, Marielle K. Weintraub, Jordon D. White, Stephanie M. Turner, Samantha L. Hodges, Amanda Leigh Morin, Lindsey N. Sadler, Gary W. Boehm, Michael J. Chumley

International Journal of Exercise Science: Conference Proceedings

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6^th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has …

Assessment Of Neutrophil Functional Activity Following Prolonged Endurance Exercise, Katsuhiko Suzuki, Kaoru Sugama, Kayo Yoshitani, Koso Shiraishi, Takashi Kometani, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori

International Journal of Exercise Science: Conference Proceedings

Introduction: Neutrophils not only play an important role in host defense by migrating to the site of infection and producing reactive oxygen species (RO S), but also mediate pathological process in inflammatory tissue damage. Therefore, it is import ant not only to assess but also modulate neutrophil activities for disease prevention. We hav e reported that exhaustive exercise causes neutrophil priming (Suzuki et al. J. Appl. Physiol. , 81, 1213-1222, 1996) which might be associated wi th muscle damage (Suzuki et al. J. Appl. Physiol. , 87, 1360-1367, 1999), but antioxidant capacity is also activated following exercise (Suzuki et al. …

Assessment Of Neutrophil Functional Activity Following Prolonged Endurance Exercise, Katsuhiko Suzuki, Kaoru Sugama, Kayo Yoshitani, Koso Shiraishi, Takashi Kometani, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori

International Journal of Exercise Science: Conference Proceedings

ntroduction: Neutrophils not only play an important role in host defense by migrating to the site of infection and producing reactive oxygen species (RO S), but also mediate pathological process in inflammatory tissue damage. Therefore, it is import ant not only to assess but also modulate neutrophil activities for disease prevention. We hav e reported that exhaustive exercise causes neutrophil priming (Suzuki et al. J. Appl. Physiol. , 81, 1213-1222, 1996) which might be associated wi th muscle damage (Suzuki et al. J. Appl. Physiol. , 87, 1360-1367, 1999), but antioxidant capacity is also activated following exercise (Suzuki et al. …

Adenosine A2b Receptor Effects On Post-Mi Remodeling And Cardiac Fibroblast Function, Enbo Zhan

Wayne State University Dissertations

Adenosine A_2B receptor (A_2BR) appear to contribute to chronic inflammation. This receptor is highly expressed in macrophages and cardiac fibroblasts, cells which play key roles in inflammation and healing following myocardial infarction (MI). A_2BR have been shown to induce collagen production and promote organ fibrosis, although the reports of A_2BR role on MI are limited and conflicting. The results of cardiac fibroblast (CF) studies however suggest that non-selective A_2BR stimulation inhibits collagen expression. The hypothesis of the present study was that deletion of A_2BR reduces adverse remodeling in post-MI, …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

Down's Syndrome, Neroinflammation, And Alzheimer Neuropathogenesis, Donna M. Wilcock, W. Sue T. Griffin

Physiology Faculty Publications

Down syndrome (DS) is the result of triplication of chromosome 21 (trisomy 21) and is the prevailing cause of mental retardation. In addition to the mental deficiencies and physical anomalies noted at birth, triplication of chromosome 21 gene products results in the neuropathological and cognitive changes of Alzheimer's disease (AD). Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that this chromosome 21 gene product was a principal neuropathogenic culprit in AD as well as DS. The discovery of …

Orofacial Neuropathic Pain Mouse Model Induced By Trigeminal Inflammatory Compression (Tic) Of The Infraorbital Nerve, Fei Ma, Liping Zhang, Danielle Lyons, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.

RESULTS: The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild …

Chronic Changes In Serum Il-6 And Tnf-Α Following 12 Weeks Of Concurrent Resistance And Aerobic Exercise Are Dependent On Exercise Mode And May Affect Adaptation, Brad S. Lambert, Justin P. Dobson, Stephen F. Crouse

International Journal of Exercise Science: Conference Proceedings

PURPOSE: To examine physiological responses to concurrent resistance and land treadmill training (RT-LTM) compared to concurrent resistance and aquatic treadmill training (RT-ATM) and the chronic effect of each on serum TNF-α and IL-6 (cytokines associated with chronic inflammation, CVD, and skeletal muscle metabolism). METHODS: Twenty-six untrained subjects (M: n=13, 98.6±17.1kg, 182.2±6.2cm, 34±11yrs, F: n=13, 78.9±14.0kg, 165.1±5.1cm, 38±11yrs) were screened to assess VO_2max, body composition (DEXA), and strength (Lifts: leg press, chest press, leg curl, lat pull, leg ext, triceps push-down, biceps curl). Subjects were then randomized into 2 groups: RT-LTM (M=6, F=7), RT-ATM (M=7, F=6). Each performed progressive …

Influence Of Fitness And Adiposity On Melanocortin-1 And Melanocortin-3 Receptors On Monocytes., Matthew Unthank, Jonathan Woodson, Jason Butler, Gregory Bratton, James Barbee, Michael Chumley, Dennis Cheek, Joel Mitchell, Melody Phillips

International Journal of Exercise Science: Conference Proceedings

Purpose: While it is known that exercise improves health by reducing systemic inflammation, potential mechanisms remain to be elucidated. The purpose of this study is to examine the influence of fitness and adiposity on the anti-inflammatory melanocortin system as a potential mechanism by which exercise reduces inflammation. Methods: Forty-one men and women (35-55yr), who were free from cardiovascular disease, inflammatory disorders, and not taking medications that affect inflammation, were recruited. Participants were questioned about exercise habits and medical history; then completed testing for body composition and aerobic fitness (VO₂max). Subjects were classified as lean/fit (LF, n=14), overweight/fit (OF, …

Effect Of Eleven Weeks Training Program On Inflammatory, Hematological And Biochemical Parameters In Rat Skeletal Muscle, Liver And Serum, Fernando Oliveira Catanho Da Silva, Rejane Lucco, Rodrigo Ferraresso, Danilo Lopes Ferrucci

International Journal of Exercise Science: Conference Proceedings

Physical exercise is known causer of acute traumas in biological structures. Chronically, physical training or can lead to a coherent sequence of traumas leading to Adaptation (Functional Overreaching – FOR) or to an imbalance between stimulus and recovery leading to Overtraining Syndrome (OTS). In the present study we analyzed muscle and hepatic cytokines concentration: Interleukin-6 (IL6), Tumor Necrose Factor-Alpha (TNF-α), Interleukin-1Beta (IL1-β) and Interleukin-10 (IL-10); muscle and serum concentration of glutamate (GLU) and glutamine (GLN); serum concentration of C-reactive Protein (CRP), Alpha-1 Glicoprotein Acid (AGA), Albumin (ALB), Uric Acid (UA), Ferric Reducing Ability of Plasma (FRAP), Creatine Kinase (CK), Red …

Nutrition, Inflammation, And Infectious Disease, Helieh S. Oz, Sung-Ling Yeh

Physiology Faculty Publications

No abstract provided.

Voluntary Wheel Running During Weight Loss Leads To Differential Changes In Monocytes, Compared To Forced Treadmill Running, Katie C. Carpenter, Kelley Strohacker, Whitney L. Breslin, Thomas W. Lowder, Brian K. Mcfarlin

International Journal of Exercise Science: Conference Proceedings

High-fat feeding and subsequent weight gain may contribute to innate immune dysfunction. Weight loss via calorie restriction and exercise represent one means to restore normal immune function. The purpose of the study was to examine how 8- weeks of aerobic exercise and low-fat diet affects weight gain, monocyte concentration, and monocyte cell-surface expression of TLR2, TLR4, CD80, and CD86. For 12- months, 24 male CD-1 mice underwent a pre-treatment phase, consuming either a low fat (10% fat) or high-fat (60% fat) diet ad libitum. Mice were randomly assigned to one of four groups (N=6/group): CN (low-fat sedentary), V-EX (voluntary wheel …

The Effects Of Chronic Prophylactic Naproxen Sodium On Skeletal Muscle Adaptation To Resistance Exercise In Recreationally-Trained College-Aged Males, Christi Brewer

Electronic Theses and Dissertations

Resistance exercise causes exercise-induced muscle injury (EIMI), triggering an acute local inflammatory response associated with delayed-onset muscle soreness (DOMS). DOMS is characterized by a predictable discomfort and decreased level of muscle performance and is believed to be the product of both mechanical and inflammatory processes. From the latter perspective, non-steroidal anti-inflammatory drugs (NSAIDs) have been investigated for their potential to alleviate DOMS-associated symptoms. Such analgesics exert their effects by blocking the formation of prostaglandins; however, prostaglandins, specifically prostaglandin F 2?, also play an important role in skeletal muscle regeneration. While some have advocated the use of NSAIDs for the relief …

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …

Delayed Wound Healing: Can Exercise Accelerate It?, K Todd Keylock, Hilary Young

International Journal of Exercise Science

Poorly healing wounds affect millions around the world, yet preventive methods and low-cost, effective treatments are few. Wounds heal quickly through well-coordinated phases in those who are healthy and active but can become chronically nonhealing as a result of disease and inactivity. Recently it has been reported that moderate aerobic exercise accelerated healing rates in the aged. High levels of inflammation are known to delay wound healing, and aging and disease are associated with chronically increased inflammation. Therefore, exercise may help speed healing by reducing inflammation to healthier levels not only in the aged, but also in other populations with …

Acid-Sensing Ion Channels And Pain, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management.

Consequences Of Weight Cycling: An Increase In Disease Risk?, Kelley Strohacker†, Katie C. Carpenter†, Brian K. Mcfarlin‡

International Journal of Exercise Science

Research indicates that weight cycling, or “yo-yo dieting” is a common occurrence in obese populations. The long term negative health consequences of weight cycling are debated and it is unclear whether or not this weight change pattern poses a greater disease risk compared to obesity maintenance. This review discusses the prevalence of weight cycling and physiological alterations occurring during weight loss that promotes weight regain. We also discuss the effect weight regain has upon adipose tissue in terms of rate and type of accumulation. Also within this review are discussions surrounding the previously published literature based upon human and rodent …

Enkephalin-Encoding Herpes Simplex Virus-1 Decreases Inflammation And Hotplate Sensitivity In A Chronic Pancreatitis Model, Hong Yang, Terry A. Mcnearney, Rong Chu, Ying Lu, Yong Ren, David C. Yeomans, Steven P. Wilson, Karin N. Westlund

Physiology Faculty Publications

Background: A chronic pancreatitis model was developed in young male Lewis rats fed a high-fat and alcohol liquid diet beginning at three weeks. The model was used to assess time course and efficacy of a replication defective herpes simplex virus type 1 vector construct delivering human cDNA encoding preproenkephalin (HSV-ENK).

Results: Most surprising was the relative lack of inflammation and tissue disruption after HSV-ENK treatment compared to the histopathology consistent with pancreatitis (inflammatory cell infiltration, edema, acinar cell hypertrophy, fibrosis) present as a result of the high-fat and alcohol diet in controls. The HSV-ENK vector delivered to the pancreatic surface …

Il-1Α And Tnf-Α Down-Regulate Crh Receptor-2 Mrna Expression In The Mouse Heart, Sarah C. Coste, Kurt A. Heldwein, Susan L. Stevens, Eric Tobar-Dupres, Mary P. Stenzel-Poore

Faculty Publications

Two receptors (CRH receptor type 1 and CRH receptor type 2) have been identified for the stress-induced neuropeptide, CRH and related peptides, urocortin, and urocortin II. We previously found marked down-regulation of cardiac CRH receptor type 2 expression following administration of bacterial endotoxin, lipopolysaccharide, a model of systemic immune activation, and inflammation. We postulated that inflammatory cytokines may regulate CRH receptor type 2. We show that systemic IL-1α administration significantly down-regulates CRH receptor type 2 mRNA in mouse heart. In addition, TNFα treatment also reduces CRH receptor type 2 mRNA expression, although the effect was not as marked as with …