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Inflammation

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Full-Text Articles in Medical Molecular Biology

Myeloid Mmp14 Couples Extracellular Proteolysis To Inflammatory And Metabolic Remodeling During Obesity, Long J Shao, Fathima Elizondo, Feng Gao, Elizabeth L Lieu, Bharati Reddi, Maryam Elizondo, Iqbal Mahmud, Kristin Eckel-Mahan, Philipp E Scherer, Xin Ge, Huaizhu Wu, Sean Hartig, Kai Sun Jul 2026

Myeloid Mmp14 Couples Extracellular Proteolysis To Inflammatory And Metabolic Remodeling During Obesity, Long J Shao, Fathima Elizondo, Feng Gao, Elizabeth L Lieu, Bharati Reddi, Maryam Elizondo, Iqbal Mahmud, Kristin Eckel-Mahan, Philipp E Scherer, Xin Ge, Huaizhu Wu, Sean Hartig, Kai Sun

The Brown Foundation: Institute of Molecular Medicine

Macrophages orchestrate tissue remodeling, inflammation, and metabolic dysfunction in obesity, but the role of macrophage-intrinsic extracellular proteolysis in immunometabolic regulation remains unclear. Matrix metalloproteinase-14 (MMP14), a membrane-bound protease, is strongly induced during monocyte-to-macrophage differentiation and further elevated in adipose tissue macrophages from high-fat diet (HFD)-fed mice. Pharmacological inhibition or myeloid-specific deletion of Mmp14 impaired macrophage differentiation, proliferation, migration, phagocytosis, and inflammatory activation in response to obesity-associated adipose tissue signals. Mechanistically, MMP14 promoted inflammatory programming by increasing endotrophin generation and enhancing TLR4-NFκB signaling. MMP14 also reprogrammed macrophage lipid metabolism by suppressing lipolysis and promoting lipid accumulation, altering metabolic communication with neighboring …


Telomerase Knockout In Myeloid Cells Predisposes Mice To Foam Cell Formation, Dyslipidemia, Lung Fibrosis, And Cardiac Dysfunction, Zhanguo Gao, Yongmei Yu, David Wiggins, Eva M Sevick-Muraca, Mikhail G Kolonin Apr 2026

Telomerase Knockout In Myeloid Cells Predisposes Mice To Foam Cell Formation, Dyslipidemia, Lung Fibrosis, And Cardiac Dysfunction, Zhanguo Gao, Yongmei Yu, David Wiggins, Eva M Sevick-Muraca, Mikhail G Kolonin

The Brown Foundation: Institute of Molecular Medicine

Aging-associated changes in myeloid cells are incompletely understood. One of the culprits of aging is the downregulation of the Tert gene coding for the catalytic subunit of telomerase. Studies of mouse models with Tert knockout (KO) in specific cells have revealed the importance of the telomere-independent noncanonical function of TERT in supporting mitochondrial metabolism and protection from cell senescence. To investigate the role of TERT in myeloid cells (MCs), we analyzed mice with Tert KO in the LysM+ lineage, indelibly labeled with membrane green fluorescent protein (mG). Macrophage numbers and properties in various organs were compared. Changes in the vasculature, …


Functional Roles Of The Complement Immune System In Cardiac Inflammation And Hypertrophy, Kathryn D Hok, Haydn E Rich, Anthony Shadid, Lavanya Gunamalai, Tingting Weng-Mills, Rajarajan A Thandavarayan, Nirmal K Banda, Marie-Francoise Doursout, Marcos I Restrepo, Pooja Shivshankar Oct 2025

Functional Roles Of The Complement Immune System In Cardiac Inflammation And Hypertrophy, Kathryn D Hok, Haydn E Rich, Anthony Shadid, Lavanya Gunamalai, Tingting Weng-Mills, Rajarajan A Thandavarayan, Nirmal K Banda, Marie-Francoise Doursout, Marcos I Restrepo, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

Cardiac inflammation and hypertrophy develop as a pathologic response to an array of insults, such as myocardial infarctions, chronic systemic hypertension, and valvular defects. Due to the high prevalence of such conditions, there is an increasing need to prevent and halt cardiac hypertrophy. Because cardiac damage and subsequent remodeling can lead to arrhythmias, heart failure, and even sudden cardiac death, inhibition of cardiac hypertrophy is key to reducing cardiovascular-related mortality. The immune system is the driving force behind inflammatory reactions. All three pathways of complement system activation-classical, lectin, and alternative-are implicated in developing cardiac damage, inflammation, and hypertrophy due to …


Identifying Novel Fibrotic Mechanisms Underlying Treatment-Resistant Lower Urinary Tract Dysfunction, Quentin Darcy Aug 2025

Identifying Novel Fibrotic Mechanisms Underlying Treatment-Resistant Lower Urinary Tract Dysfunction, Quentin Darcy

Graduate Doctoral Dissertations

ABSTRACT

IDENTIFYING NOVEL FIBROTIC MECHANISMS UNDERLYING TREATMENT-RESISTANT LOWER URINARY TRACT DYSFUNCTION

August 2025

Quentin D’Arcy, B.S., University of Massachusetts Amherst

Ph.D., University of Massachusetts Boston

Directed by Dr. Jill Macoska

Lower urinary tract dysfunction (LUTD) is a common, age-related disease that affects millions of men over the age of 50. Current treatment for this and other related prostate diseases concentrate on decreasing benign prostate growth and relaxing smooth muscle contractions to alleviate urinary voiding symptoms. However, up to 45% of patients with LUTD are treatment-resistant and require surgical intervention to resolve prostate issues. By focusing on the contribution of inflammation-derived …


Reevaluating Anti-Inflammatory Therapy: Targeting Senescence To Balance Anti-Cancer Efficacy And Vascular Disease, Bernardo Casso-Chapa, Norma Alicia Vazquez González, Nhat-Tu Le, Nicolas L Palaskas, Kevin T Nead, Lydia P Eutsey, Venkata S K Samanthapudi, Abigail M Osborn, Jonghae Lee, Gilbert Mejia, Oanh Hoang, Steven H Lin, Anita Deswal, Joerg Herrmann, Guangyu Wang, James L Kirkland, Sunil Krishnan, Xander H T Wehrens, Eduardo N Chini, Syed Wamique Yusuf, Cezar A Iliescu, Abhishek Jain, Jared K Burks, Erin Seeley, Philip L Lorenzi, Khanh M Chau, Keila C Ostos-Mendoza, Isabella M Grumbach, Paul S Brookes, Nordin M J Hanssen, Menno P J De Winther, Laurent Yvan-Charvet, Sivareddy Kotla, Keri Schadler, Jun-Ichi Abe Mar 2025

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence To Balance Anti-Cancer Efficacy And Vascular Disease, Bernardo Casso-Chapa, Norma Alicia Vazquez González, Nhat-Tu Le, Nicolas L Palaskas, Kevin T Nead, Lydia P Eutsey, Venkata S K Samanthapudi, Abigail M Osborn, Jonghae Lee, Gilbert Mejia, Oanh Hoang, Steven H Lin, Anita Deswal, Joerg Herrmann, Guangyu Wang, James L Kirkland, Sunil Krishnan, Xander H T Wehrens, Eduardo N Chini, Syed Wamique Yusuf, Cezar A Iliescu, Abhishek Jain, Jared K Burks, Erin Seeley, Philip L Lorenzi, Khanh M Chau, Keila C Ostos-Mendoza, Isabella M Grumbach, Paul S Brookes, Nordin M J Hanssen, Menno P J De Winther, Laurent Yvan-Charvet, Sivareddy Kotla, Keri Schadler, Jun-Ichi Abe

The Brown Foundation: Institute of Molecular Medicine

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression. Anti-inflammatory therapy, therefore, presents a unique dilemma for cancer survivors: while it may decrease cardiovascular risk, it might also promote cancer growth and metastasis by suppressing the immune response. Senescence presents a potentially targetable solution to this challenge; senescence increases the risk of both cancer therapy resistance and vascular disease. Exercise, notably, shows promise in delaying this premature senescence, potentially …


Aging- And Alcohol-Associated Spatial Transcriptomic Signature In Mouse Acute Pancreatitis Reveals Heterogeneity Of Inflammation And Potential Pathogenic Factors, Jiajing Li, Qiang Shen, Jennifer M Bailey-Lundberg, Zhongming Zhao, Daniel Kraushaar, Patricia Castro, Yanna Cao, W Jim Zheng, Tien C Ko Jun 2024

Aging- And Alcohol-Associated Spatial Transcriptomic Signature In Mouse Acute Pancreatitis Reveals Heterogeneity Of Inflammation And Potential Pathogenic Factors, Jiajing Li, Qiang Shen, Jennifer M Bailey-Lundberg, Zhongming Zhao, Daniel Kraushaar, Patricia Castro, Yanna Cao, W Jim Zheng, Tien C Ko

Faculty, Staff and Student Publications

The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via …


Development Of A Synthetic Biomarker System For Early Detection Of Ischemic Stroke, Mason L. Matthies May 2024

Development Of A Synthetic Biomarker System For Early Detection Of Ischemic Stroke, Mason L. Matthies

Honors Thesis

Stroke, particularly Ischemic Stroke (IS) affects millions of individuals across the world each year . Current diagnostic methods like CT scans and MRI imaging have limitations in detecting minor IS due to the limited spatial resolution of the CT scan and the feasibility and access to MRIs warranting a more effective method of early detection. Natural biomarkers are currently ineffective in detecting IS prior to severe damage like rapid cell death (32,000 cells/sec) post arterial blockage because there is minimal amount of natural biomarkers expressed from minor cellular damage . Our proposed Synthetic Biomarker System (SBS) would solve this by …


Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu Jan 2024

Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …


Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson Jan 2024

Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson

Electronic Theses & Dissertations (2024 - present)

Fibrosis is of significant concern to the medical community as numerous disease processes are characterized by progressive fibrosis leading to organ damage. We begin the process of examining the mechanism of fibrosis to salivary gland hypofunction and briefly consider Sjögren’s Disease (SjD). Method: We employed single-cell RNA sequencing data from a reversible mouse salivary gland injury model and from NOD/ShiLtJ mice, a model of secondary SjD. We performed treatment comparisons with the help of Seurat dotplots and UMAPS. Using differential gene expression analysis and the publicly available R packages: clusterProfiler, WikiPathways and Cytoscape, we identified the processes and pathways …


Exploring The Impact Of P2y2 Receptor Activation And Inflammation On Glucose Homeostasis In Mice, Jamila Makhloufi Jan 2024

Exploring The Impact Of P2y2 Receptor Activation And Inflammation On Glucose Homeostasis In Mice, Jamila Makhloufi

Graduate Theses/Dissertations

Insulin resistance is the body's impaired ability to utilize endogenous and exogenous insulin to take up blood glucose and is associated with many clinical conditions including type 2 diabetes, hypertension, obesity, and cardiovascular disease. The cause of insulin resistance is still unknown; however, it is linked to inflammation. The activation of the purinergic P2Y2 receptor potentiates an inflammatory response under the pathogenesis of obesity and has adverse effects on glucose metabolism by regulating insulin resistance. The goal of this research is to investigate the effects of P2Y2 receptor activation on the downstream signaling pathways of the insulin receptor …


A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Silvia Lonardi, Matilde Monti, Francesco Missale, Changxu Fan, Matthew L Coates, Mattia Bugatti, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Daniele Moratto, Stefania Zini, Lingjia Kong, Jacques Deguine, Mark E Peeples, Ramnik J Xavier, Menna R Clatworthy, Ting Wang, Marina Cella, William Vermi, Marco Colonna Dec 2023

A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Silvia Lonardi, Matilde Monti, Francesco Missale, Changxu Fan, Matthew L Coates, Mattia Bugatti, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Daniele Moratto, Stefania Zini, Lingjia Kong, Jacques Deguine, Mark E Peeples, Ramnik J Xavier, Menna R Clatworthy, Ting Wang, Marina Cella, William Vermi, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. …


A Network Pharmacology And Molecular-Docking-Based Approach To Identify The Probable Targets Of Short-Chain Fatty-Acid-Producing Microbial Metabolites Against Kidney Cancer And Inflammation, Md Rezaul Karim, Md Niaj Morshed, Safia Iqbal, Shahnawaz Mohammad, Ramya Mathiyalagan, Yeon Ju Kim, Dong Uk Yang Nov 2023

A Network Pharmacology And Molecular-Docking-Based Approach To Identify The Probable Targets Of Short-Chain Fatty-Acid-Producing Microbial Metabolites Against Kidney Cancer And Inflammation, Md Rezaul Karim, Md Niaj Morshed, Safia Iqbal, Shahnawaz Mohammad, Ramya Mathiyalagan, Yeon Ju Kim, Dong Uk Yang

Faculty, Staff and Student Publications

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species …


Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Jingjing Zhang, He Huang Nov 2023

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Jingjing Zhang, He Huang

Faculty, Staff and Student Publications

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …


Updates On The Immune Cell Basis Of Hepatic Ischemia-Reperfusion Injury, Kang Ho Kim Sep 2023

Updates On The Immune Cell Basis Of Hepatic Ischemia-Reperfusion Injury, Kang Ho Kim

Faculty, Staff and Student Publications

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been …


Peran Penting Inflamasom Nlrp3 Pada Aterosklerosis, Dewi Sukmawati Jun 2023

Peran Penting Inflamasom Nlrp3 Pada Aterosklerosis, Dewi Sukmawati

Jurnal Penyakit Dalam Indonesia

Cardiovascular diseases (CVDs) still contribute as the main cause of mortality and premature mortality worldwide. In Indonesia, CVDs contribute to 35% of the main cause of death in non-communicable diseases followed by diabetes at 6%. The ischemic heart disease and acute ischemic stroke is the main cause of death in Indonesia due to atherosclerosis. Atherosclerosis is a multifactorial cause, with chronic inflammation which causes myocardial infarction and acute ischemic stroke. Research demonstrated that one of the underlying mechanisms of atherosclerosis is inflammation. The current research suggested that inflammation could activate a complex of cytosol proteins, namely nucleotide-binding oligomerization domain-like receptor …


Immunometabolic Reprogramming, Another Cancer Hallmark, Vijay Kumar, John H. Stewart May 2023

Immunometabolic Reprogramming, Another Cancer Hallmark, Vijay Kumar, John H. Stewart

School of Medicine Faculty Publications

Molecular carcinogenesis is a multistep process that involves acquired abnormalities in key biological processes. The complexity of cancer pathogenesis is best illustrated in the six hallmarks of the cancer: (1) the development of self-sufficient growth signals, (2) the emergence of clones that are resistant to apoptosis, (3) resistance to the antigrowth signals, (4) neo-angiogenesis, (5) the invasion of normal tissue or spread to the distant organs, and (6) limitless replicative potential. It also appears that non-resolving inflammation leads to the dysregulation of immune cell metabolism and subsequent cancer progression. The present article delineates immunometabolic reprogramming as a critical hallmark of …


Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao May 2023

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …


The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling Apr 2023

The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling

Faculty, Staff and Student Publications

Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS-STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS-STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining …


Interplay Between Liver Type 1 Innate Lymphoid Cells And Nk Cells Drives The Development Of Alcoholic Steatohepatitis, Linxi Xie, Huiru Zhang, Xuan Wang, Hongyu Wu, Jingjing Xu, Li Gui, Bao Li, Cynthia Ju, Hui Peng, Shi Yin, Long Xu Jan 2023

Interplay Between Liver Type 1 Innate Lymphoid Cells And Nk Cells Drives The Development Of Alcoholic Steatohepatitis, Linxi Xie, Huiru Zhang, Xuan Wang, Hongyu Wu, Jingjing Xu, Li Gui, Bao Li, Cynthia Ju, Hui Peng, Shi Yin, Long Xu

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Liver contains high frequency of group 1 innate lymphoid cells (ILC), which are composed of comparable number of type 1 ILC (ILC1) and natural killer (NK) cells in steady state. Little is known about whether and how the interaction between ILC1 and NK cells affects the development of alcoholic liver disease.

METHODS: A mouse model of chronic alcohol abuse plus single-binge (Gao-Binge model) was established. The levels of alanine aminotransferase/aspartate aminotransferase, hepatic lipid, and inflammatory cytokines or neutrophils were measured to evaluate the degree of liver injury, steatosis, and inflammation. Flow cytometric analysis, cell depletion, or adoptive …


Dysregulated Coagulation System Links To Inflammation In Diabetic Kidney Disease, Wenyu Gong Jan 2023

Dysregulated Coagulation System Links To Inflammation In Diabetic Kidney Disease, Wenyu Gong

Faculty, Staff and Student Publications

Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease worldwide. Despite extensive research, the exact mechanisms responsible for its development remain incompletely understood. Notably, patients with diabetes and impaired kidney function exhibit a hypercoagulable state characterized by elevated levels of coagulation molecules in their plasma. Recent studies propose that coagulation molecules such as thrombin, fibrinogen, and platelets are interconnected with the complement system, giving rise to an inflammatory response that potentially accelerates the progression of DKD. Remarkably, investigations have shown that inhibiting the coagulation system may protect the kidneys in various animal models and clinical trials, suggesting …


The Genetic Landscape And Clinical Implication Of Pediatric Moyamoya Angiopathy In An International Cohort, Jian-Zhuang Li Jan 2023

The Genetic Landscape And Clinical Implication Of Pediatric Moyamoya Angiopathy In An International Cohort, Jian-Zhuang Li

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …


Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Eszter K Vladar, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig Dec 2022

Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Eszter K Vladar, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during …


Ccl4 Regulates Eosinophil Activation In Eosiccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammationnophilic Airway Inflammation, Linh Manh Nguyen, Akira Kanda, Hiroshi Iwai Dec 2022

Ccl4 Regulates Eosinophil Activation In Eosiccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammationnophilic Airway Inflammation, Linh Manh Nguyen, Akira Kanda, Hiroshi Iwai

Faculty, Staff and Student Publications

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in …


The Innate Immune System In Cardiovascular Diseases And Its Role In Doxorubicin-Induced Cardiotoxicity, Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman Nov 2022

The Innate Immune System In Cardiovascular Diseases And Its Role In Doxorubicin-Induced Cardiotoxicity, Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release …


Exploratory Investigation Of The Plasma Proteome Associated With The Endotheliopathy Of Trauma, Erwin M Schoof, Claudia Pedroza, Charles E Wade Jun 2022

Exploratory Investigation Of The Plasma Proteome Associated With The Endotheliopathy Of Trauma, Erwin M Schoof, Claudia Pedroza, Charles E Wade

Faculty, Staff and Student Publications

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma.

Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry.

Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) …


Editorial: The Role Of Hmgb1 In Immunity, M. Son, B. Diamond, J. Shin Jan 2020

Editorial: The Role Of Hmgb1 In Immunity, M. Son, B. Diamond, J. Shin

Journal Articles

No abstract provided.


It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown Dec 2019

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

Graduate Theses/Dissertations

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …


Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin May 2019

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …


Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, K. R. Lehner, H. A. Silverman, M. E. Adorissio, A. Roy, A. Al-Onaizi, S. S. Chavan, Y. Al-Abed, C. N. Metz, K. J. Tracey, V. A. Paviov, +6 Additional Authors Jan 2019

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, K. R. Lehner, H. A. Silverman, M. E. Adorissio, A. Roy, A. Al-Onaizi, S. S. Chavan, Y. Al-Abed, C. N. Metz, K. J. Tracey, V. A. Paviov, +6 Additional Authors

Journal Articles

No abstract provided.


Persons With Chronic Spinal Cord Injury Have Decreased Natural Killer Cell And Increased Toll-Like Receptor/Inflammatory Gene Expression, P. Herman, A. Stein, K. Gibbs, I. Korsunsky, P. Gregersen, O. Bloom Jan 2018

Persons With Chronic Spinal Cord Injury Have Decreased Natural Killer Cell And Increased Toll-Like Receptor/Inflammatory Gene Expression, P. Herman, A. Stein, K. Gibbs, I. Korsunsky, P. Gregersen, O. Bloom

Journal Articles

No abstract provided.