A5081904364- Asthma and respiratory diseases
- Respiratory and Cough-Related Research
- Neuroscience of respiration and sleep
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory viral infections research
- Neuropeptides and Animal Physiology
- Pediatric health and respiratory diseases
- Eosinophilic Disorders and Syndromes
- Ion Channels and Receptors
- Regulation of Appetite and Obesity
- Heart Rate Variability and Autonomic Control
- Neuroendocrine regulation and behavior
- Neurogenetic and Muscular Disorders Research
- Immune Cell Function and Interaction
- Nutrition, Genetics, and Disease
- Exercise and Physiological Responses
- Biochemical Analysis and Sensing Techniques
- IL-33, ST2, and ILC Pathways
- Adipose Tissue and Metabolism
- Amyotrophic Lateral Sclerosis Research
- Cellular Mechanics and Interactions
- Fatty Acid Research and Health
- RNA regulation and disease
- Healthcare and Venom Research
- Cell Adhesion Molecules Research
Oregon Health & Science University
2016-2025
Oregon Health and Science University Hospital
2024
University of Portland
2008
University of Pennsylvania
2002-2006
In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter function eosinophilia present in 50 60% of asthmatics. However, the effects on structure have not been established. We tested whether measured physiological consequences those changes. Our results humans with without eosinophilic asthma showed innervation substance P expression were increased moderate persistent asthmatics compared mild intermittent healthy...
Obesity is a substantial risk factor for developing asthma, but the molecular mechanisms underlying this relationship are unclear. We tested role of insulin in airway responsiveness to nerve stimulation using rats genetically prone or resistant diet-induced obesity. Airway response vagus and M2 M3 muscarinic receptor function were measured obese-prone -resistant with high low circulating insulin. The effects on nerve-mediated human smooth muscle contraction vitro. Our data show that...
Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in airways of 60-70% patients with asthma, we evaluated effects on a common respiratory virus, parainfluenza 1, lung. Eosinophils recruited to wild-type mice after ovalbumin sensitization and challenge significantly decreased virus RNA lungs 4 days infection compared nonsensitized animals. This antiviral effect was also seen IL-5 transgenic an abundance airway (NJ.1726) but lost...
The impact of diet-induced maternal obesity on offspring airway hyperresponsiveness was studied in a diversity outbred mouse model that mirrors human genetic diversity. Female mice were started high-fat or regular diet 8 weeks before breeding and throughout pregnancy lactation. After weaning, all fed diet. By 12 weeks, body weight fat increased diet–fed dams, which accompanied by metabolic dysfunction hyperinsulinemia. This followed epithelial sensory innervation bronchoconstriction to...
Focal adhesion kinase (FAK) is a protein-tyrosine that associates with multiple cell surface receptors and signaling proteins through which it can modulate the activity of several intracellular pathways. FAK influence formation distinct actin cytoskeletal structures such as lamellipodia stress fibers in part effects on small Rho GTPases, although molecular interconnections these events are not well defined. Here, we report interacts p190RhoGEF, RhoA-specific GDP/GTP exchange factor, neuronal...
Resistin levels are increased in obesity, and hyperresistinemia impairs glucose homeostasis rodents. Here, we have determined the role of resistin ob/ob mice that obese insulin resistant because genetic deficiency leptin. Loss obesity by further lowering metabolic rate without affecting food intake. Nevertheless, improved tolerance sensitivity these severely mice, largely enhancing insulin-mediated disposal muscle adipose tissue. In contrast, C57BL/6J with diet-induced but wild-type leptin...
Prenatal cannabis use is rising, in part due to legalization and perceptions of safety. The impact prenatal exposure on offspring development, especially respiratory health, remains largely unknown. objective this study was determine whether utero delta-9-tetrahydrocannabinol (THC), the main psychoactive component cannabis, deleterious lung development function using a rhesus macaque model. Female macaques received daily edible containing either THC (2.5 mg/7 kg/day, equivalent heavy medical...
Infections with respiratory viruses induce exacerbations of asthma, increase acetylcholine release and potentiate vagally mediated bronchoconstriction by blocking inhibitory M₂ muscarinic receptors on parasympathetic neurons. Here we test whether virus-induced receptor dysfunction airway hyperresponsiveness are tumour necrosis factor-alpha (TNF-α) dependent.Guinea pigs were pretreated etanercept or phosphate-buffered saline 24 h before intranasal infection parainfluenza. Four days later,...
Children born to obese mothers are prone develop asthma and airway hyperresponsiveness, but the mechanisms behind this unclear. Here we developed a mouse model of maternal diet-induced obesity that recapitulates metabolic abnormalities seen in humans mothers. Offspring dams fed high-fat diet (HFD) showed increased adiposity, hyperinsulinemia, insulin resistance at 16 wk age despite being only regular (RD). Bronchoconstriction induced by inhaled 5-hydroxytriptamine was also significantly...
Increased tumour necrosis factor-alpha (TNF-alpha) is associated with airway hyperreactivity in antigen-challenged animals. In human asthmatics, TNF-alpha increased and blocking it prevents some asthmatic patients. However, the mechanisms by which mediates are unknown. Airway can be caused dysfunction of neuronal M(2) muscarinic receptors that normally limit acetylcholine release from parasympathetic nerves. Here we test whether etanercept receptor guinea pigs.Ovalbumin-sensitized pigs were...
Obesity increases incidence and severity of asthma but the molecular mechanisms are not completely understood. Hyperinsulinemia potentiates vagally induced bronchoconstriction in obese rats. Since results from airway smooth muscle contraction, we tested whether insulin changed agonist-induced contraction. Obesity-prone resistant rats were fed a low-fat diet for 5 wk treated with (Lantus, 3 units/rat sc) 16 h before was measured. Ex vivo, contractile responses to methacholine measured...
Obesity-induced asthma responds poorly to all current pharmacological interventions, including steroids, suggesting that classic, eosinophilic inflammation is not a mechanism. Since insulin resistance and hyperinsulinemia are common in obese individuals associated with increased risk of asthma, we used diet-induced mice study how induces airway hyperreactivity. Inhaled 5-HT or methacholine induced dose-dependent bronchoconstriction was significantly potentiated mice. Cutting the vagus nerves...
Studies of experimental motor neuron degeneration attributable to expression neurofilament light chain (NF-L) transgenes have raised the possibility that neuropathic effects result from overexpression NF-L mRNA, independent protein (Cañete-Soler et al., 1999). The present study was undertaken test for an RNA-mediated pathogenesis. Transgenic mice were derived using either enhanced green fluorescent reporter construct or modified chimeric constructs differ only in their 3' untranslated...
Increased insulin is associated with obesity-related airway hyperreactivity and asthma. We tested whether the use of metformin, an antidiabetic drug used to reduce resistance, can circulating insulin, thereby preventing in rats dietary obesity. Male female were fed a high- or low-fat diet for 5 wk. Some male simultaneously treated metformin (100 mg/kg orally). In separate experiments, after wk high-fat diet, some switched whereas others continued additional Bronchoconstriction bradycardia...
Eosinophils mediate airway hyperresponsiveness by increasing vagally mediated reflex bronchoconstriction. Here, we tested whether circulating or eosinophils change nerve function. Airway resistance in response to aerosolized 5-hydroxytryptamine (5-HT, 10–300 mM) was measured wild-type mice transgenic that overexpress IL5 T cells (+IL5 ), epithelium AE but are devoid of /−Eos). Inflammatory bronchoalveolar lavage (BAL), blood, and bone marrow were quantified. Blood increased +IL5 compared...
Obesity-related asthma often presents with more severe symptoms than non-obesity-related and responds poorly to current treatments. Both insulin resistance hyperinsulinemia are common in obesity. We have shown that increased mediates airway hyperreactivity diet-induced obese rats by causing neuronal M 2 muscarinic receptor dysfunction, which normally inhibits acetylcholine release from parasympathetic nerves. Decreasing streptozotocin prevented dysfunction. The objective of the present study...
Eosinophils contribute to metabolic homeostasis and airway hyperresponsiveness, but their specific role in obesity-related hyperresponsiveness remains unclear. To address this, we utilized transgenic mice that overexpress interleukin-5 (IL-5) peripheral T cells (+IL-5T) wild type controls. On a normal diet, +IL-5T have similar body weight, fat, nerve-mediated reflex bronchoconstriction response inhaled serotonin. Feeding 61.6% high-fat diet resulted significantly increased fasting glucose,...
The enhancement of RNA-mediated motor neuron degeneration in transgenic mice by mutating a major mRNA instability determinant light neurofilament (NF-L) transgene implicates cognate RNA binding factors the pathogenesis degeneration. p190RhoGEF is neuron-enriched guanine exchange factor (GEF) that binds to NF-L-destabilizing element, c-Jun N-terminal kinase-interactive protein-1 (JIP-1), and 14-3-3 may link expression pathways affecting neuronal homeostasis. This study was undertaken identify...
Background Major basic protein released from eosinophils to airway parasympathetic nerves blocks inhibitory M2 muscarinic receptors on the nerves, increasing acetylcholine release and potentiating reflex bronchoconstriction. Recruitment of neurons requires neural expression both intercellular adhesion molecular-1 (ICAM-1) eotaxin. We have shown that inflammatory cytokines induce eotaxin ICAM-1 in neurons. Objective To test whether β2 agonist albuterol, which is used treat asthma, changes...
The mechanisms whereby mutant gene expression triggers neurodegeneration are poorly understood but have generally been attributed to translated products. We now demonstrate direct neuropathic effects of untranslated RNA on cultured motor neurons. show that light neurofilament (NF-L) sequence in the 3′UTR an EGFP transgene (pEGFP/NF-L RNA) or a separate vector (pRc/NF-L causes dose-dependent, neuron-specific neuron degeneration. Neither unfused protein (pEGFP/wt) nor EGFP-tagged NF-L protein)...