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Articles 1 - 12 of 12
Full-Text Articles in Translational Medical Research
Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala
Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala
Center for Translational Medicine Faculty Papers
Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …
Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande
Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande
Center for Translational Medicine Faculty Papers
Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …
Anxiolytics For Bronchodilation: Refinements To Gaba, Ajay P Nayak, Steven S An
Anxiolytics For Bronchodilation: Refinements To Gaba, Ajay P Nayak, Steven S An
Department of Medicine Faculty Papers
No abstract provided.
Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn
Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn
Division of Pulmonary and Critical Care Medicine Faculty Papers
The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …
The Odorant Receptor Or2w3 On Airway Smooth Muscle Evokes Bronchodilation Via A Cooperative Chemosensory Tradeoff Between Tmem16a And Cftr., Jessie Huang, Hong Lam, Cynthia Koziol-White, Nathachit Limjunyawong, Donghwa Kim, Nicholas Kim, Nikhil Karmacharya, Premraj Rajkumar, Danielle Firer, Nicholas M Dalesio, Joseph Jude, Richard C Kurten, Jennifer L Pluznick, Deepak A. Deshpande, Raymond B Penn, Stephen B Liggett, Reynold A Panettieri, Xinzhong Dong, Steven S An
The Odorant Receptor Or2w3 On Airway Smooth Muscle Evokes Bronchodilation Via A Cooperative Chemosensory Tradeoff Between Tmem16a And Cftr., Jessie Huang, Hong Lam, Cynthia Koziol-White, Nathachit Limjunyawong, Donghwa Kim, Nicholas Kim, Nikhil Karmacharya, Premraj Rajkumar, Danielle Firer, Nicholas M Dalesio, Joseph Jude, Richard C Kurten, Jennifer L Pluznick, Deepak A. Deshpande, Raymond B Penn, Stephen B Liggett, Reynold A Panettieri, Xinzhong Dong, Steven S An
Center for Translational Medicine Faculty Papers
The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca2+]i) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated …
Obesity And Obstructive Airways Disease: Clinical Correlates And Therapeutic Considerations, John Magagna, Cali Loblundo, Raymond B. Penn, Deepak A. Deshpande, Ajay P. Nayak
Obesity And Obstructive Airways Disease: Clinical Correlates And Therapeutic Considerations, John Magagna, Cali Loblundo, Raymond B. Penn, Deepak A. Deshpande, Ajay P. Nayak
Student Papers, Posters & Projects
Obese patients are more likely to suffer from severe asthma symptoms and less likely to be able to control them. In obese patients, there is evidence that shows decreased efficacy of inhaled corticosteroids and beta-2 adrenergic agonists, the core treatment options for achieving and maintaining asthma control. This may be due to mechanical reasons like decreased ventilation and medication delivery, but there are many more pathologies of obesity that interact with pathways of both asthma pathology and asthma control. This review explores the epidemiological significance of obesity, many physiological changes in patients with obesity, the physiological interactions of asthma and …
Perinatal Nicotine With Or Without Early Life Influenza Infection Leads To Lung Dysfunction With Age., Ryan Carroll Mcallister
Perinatal Nicotine With Or Without Early Life Influenza Infection Leads To Lung Dysfunction With Age., Ryan Carroll Mcallister
Electronic Theses and Dissertations
Obstructive Airway Diseases (OADs) affect millions of people worldwide, and are characterized by chronic inflammation and tissue remodeling in the lung. It has been proposed that the development of OAD is greatly influenced (and perhaps pre-determined) by early life events, such as maternal smoking or a viral infection. However, direct evidence of this is limited and the mechanisms involved remain unclear. Our laboratory previously developed a murine model of perinatal nicotine exposure, and reported that nicotine leads to airway remodeling and decreased pulmonary function in the offspring. We discovered these effects were mediated through the α7 nicotinic acetylcholine receptor (nAChR). …
Pepducins As A Potential Treatment Strategy For Asthma And Copd., Reynold A. Panettieri, Tonio Pera, Stephen B B. Liggett, Jeffrey L. Benovic, Raymond B. Penn
Pepducins As A Potential Treatment Strategy For Asthma And Copd., Reynold A. Panettieri, Tonio Pera, Stephen B B. Liggett, Jeffrey L. Benovic, Raymond B. Penn
Center for Translational Medicine Faculty Papers
Current therapies to treat asthma and other airway diseases primarily include anti-inflammatory agents and bronchodilators. Anti-inflammatory agents target trafficking and resident immunocytes and structural cells, while bronchodilators act to prevent or reverse shortening of airway smooth muscle (ASM), the pivotal tissue regulating bronchomotor tone. Advances in our understanding of the biology of G protein-coupled receptors (GPCRs) and biased agonism offers unique opportunities to modulate GPCR function that include the use of pepducins and allosteric modulators. Recent evidence suggests that small molecule inhibitors of Gα q as well as pepducins targeting G q -coupled receptors can broadly inhibit contractile agonist-induced ASM …
New Targets For Resolution Of Airway Remodeling In Obstructive Lung Diseases., Ajay P. Nayak, Deepak A. Deshpande, Raymond B. Penn
New Targets For Resolution Of Airway Remodeling In Obstructive Lung Diseases., Ajay P. Nayak, Deepak A. Deshpande, Raymond B. Penn
Center for Translational Medicine Faculty Papers
Airway remodeling (AR) is a progressive pathological feature of the obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). The pathology manifests itself in the form of significant, progressive, and (to date) seemingly irreversible changes to distinct respiratory structural compartments. Consequently, AR correlates with disease severity and the gradual decline in pulmonary function associated with asthma and COPD. Although current asthma/COPD drugs manage airway contraction and inflammation, none of these effectively prevent or reverse features of AR. In this review, we provide a brief overview of the features and putative mechanisms affecting AR. We further discuss recently proposed …
Autophagy And Airway Fibrosis: Is There A Link?, Pawan K. Sharma, Anudeep Kota, Deepak A. Deshpande, Mehra Haghi, Brian G. Oliver
Autophagy And Airway Fibrosis: Is There A Link?, Pawan K. Sharma, Anudeep Kota, Deepak A. Deshpande, Mehra Haghi, Brian G. Oliver
Center for Translational Medicine Faculty Papers
In the past decade, an emerging process named “autophagy” has generated intense interest in many chronic lung diseases. Tissue remodeling and fibrosis is a common feature of many airway diseases, and current therapies do not prevent or reverse these structural changes. Autophagy has evolved as a conserved process for bulk degradation and recycling of cytoplasmic components to maintain basal cellular homeostasis and healthy organelle populations in the cell. Furthermore, autophagy serves as a cell survival mechanism and can also be induced by chemical and physical stress to the cell. Accumulating evidence demonstrates that autophagy plays an essential role in vital …
Mt1a Mrna Expression In Human Lung Cells (Beas 2b) After Airborne Pm10 And Copper Exposure: A Possible Biomarker For Asthma, Mariela Rosa-Casillas, Noé Crespo-Hernández, Bs, Mario Ortiz-Martínez, Braulio Jiménez-Vélez
Mt1a Mrna Expression In Human Lung Cells (Beas 2b) After Airborne Pm10 And Copper Exposure: A Possible Biomarker For Asthma, Mariela Rosa-Casillas, Noé Crespo-Hernández, Bs, Mario Ortiz-Martínez, Braulio Jiménez-Vélez
Journal of Health Disparities Research and Practice
Puerto Ricans have the highest prevalence, morbidity and mortality of asthma than any other ethnic group in the U.S. and can be triggered by different stimuli such as airborne Particle pollution (PM). PM transfers transition metals, including cooper, to the human airways generating reactive oxygen species (ROS). Metallothionein protein (MT1A) is a free radical scavenger expected to be induced in lung cells by PM exposure; however, this has never been proven nor demonstrated. The hypothesis involves the amounts of PM10 in 2004, which would be significantly higher in the urban sites during months of March and June, thereby increasing …
The Interplay Of Obesity And Asthma, James Plumb, Rickie Brawer, Nancy Brisbon
The Interplay Of Obesity And Asthma, James Plumb, Rickie Brawer, Nancy Brisbon
Department of Family & Community Medicine Faculty Papers
The relationships, interactions, and association between obesity and asthma are complex, and are active sources of hypotheses and research. An association between obesity and asthma has been reported in many studies, although considerable debate about the existence of the association and its meaning still exists. Potential associative relationships may result from genetics, immune system modifications, and mechanical mechanisms. The rising prevalence of asthma and obesity in children and adults, and the significant morbidity from both, makes it imperative that clinicians recognize the importance of weight management in patients with and without asthma.