A5080316460- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Inhalation and Respiratory Drug Delivery
- Asthma and respiratory diseases
- Respiratory viral infections research
- Influenza Virus Research Studies
- Pulmonary Hypertension Research and Treatments
- Sarcoidosis and Beryllium Toxicity Research
- Immune Response and Inflammation
- Fibroblast Growth Factor Research
- Respiratory and Cough-Related Research
- Occupational exposure and asthma
- Histiocytic Disorders and Treatments
- Medical Imaging and Pathology Studies
- S100 Proteins and Annexins
Yale University
2022-2025
Host response aimed at eliminating the infecting pathogen, as well pathogen itself, can cause tissue injury. Tissue injury leads to release of a myriad cellular components including mitochondrial DNA, which host senses through pattern recognition receptors. How sensing by shapes anti-pathogen remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), binds unmethylated CpG DNA sequences such those present bacterial and DNA. To avoid direct...
Idiopathic pulmonary fibrosis is increasingly associated with nerve-driven processes and endogenous innate immune ligands such as mitochondrial DNA (mtDNA). Interestingly, a connection between these entities has not been explored. Here, we report that noradrenaline (NA) derived from the lung's adrenergic nerve supply drives α-smooth muscle actin (αSMA)-expressing fibroblast accumulation via mechanisms involving α1 adrenoreceptors mtDNA. Using bleomycin model, compared ablation of surgical...
Abstract Host response aimed at eliminating the infecting pathogen, as well pathogen itself, can cause tissue injury. Tissue injury leads to release of a myriad cellular components including mitochondrial DNA, which host senses through pattern recognition receptors. How sensing by shapes anti-pathogen remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), binds unmethylated CpG DNA sequences such those present bacterial and DNA. To avoid...
Introduction The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation abnormal extracellular matrix, which is partly result an imbalance in collagen synthesis, cross-linking and degradation. During this process, fragments or neoepitopes, are released into circulation. significance these circulating neoepitopes remains unknown. Methods We employed plasma samples from patients with enrolled A Case Control Etiologic Study Sarcoidosis (ACCESS) Genomic Research...
Abstract Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, increasingly linked with catecholamines such as adrenaline (AD) noradrenaline (NA), hormones aldosterone (ALD). The essential functions of adrenal glands include production numerous hormones, but contribution to remains less well studied. Here, we characterized impact surgical ablation in bleomycin model fibrosis. Wild type mice underwent adrenalectomy or sham...
The lungs of patients with Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD) contain inflammatory myofibroblasts arising in association fibrotic stimuli and perturbed innate immunity. immune DNA binding receptor Cyclic GMP-AMP synthase (cGAS) is implicated inflammation fibrosis, but its involvement SSc-ILD remains unknown. We examined cGAS expression, activity, therapeutic potential using cultured fibroblasts, precision cut lung slices (PCLS), a well-accepted animal model.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which current treatment options only slow clinical progression. Previously, we identified subset of patients with IPF an accelerated course associated fibroblast expression Toll-Like Receptor 9 (TLR9) mediated by interactions its ligand mitochondrial DNA (mtDNA).
Tissue fibrosis contributes to pathology in vital organs including the lung. Curative therapies are scant. Myofibroblasts, pivotal effector cells tissue fibrosis, accumulate via incompletely understood interactions with their microenvironment. In an investigative platform grounded experimental lung biology, we find that sympathetic innervation stimulates fibrotic remodeling noradrenergic α1-adrenergic receptor engagement myofibroblasts. We demonstrate anti-fibrotic potential of targeted...
Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, increasingly linked with catecholamines such as adrenaline (AD) noradrenaline (NA), hormones aldosterone (ALD). The essential functions of adrenal glands include production numerous hormones, but contribution to remains less well studied. Here, we characterized impact surgical ablation in bleomycin model fibrosis. Wild type mice underwent adrenalectomy or sham surgery...
Abstract Pulmonary Fibrosis is a progressive and incurable condition that complicates many disease states. Adrenergic hyperinnervation accumulation of fibroblasts expressing ⍺ 1 -adrenoreceptors have been implicated in this process. Previous studies demonstrated systemic treatment with an antagonist attenuates fibrotic endpoints lung fibrosis models. In attempt to develop targeted therapy, we determined whether antagonism delivered via inhaled administration terazosin exerts antifibrotic...
ABSTRACT Idiopathic Pulmonary Fibrosis is increasingly associated with adrenergic innervation and endogenous innate immune ligands such as mitochondrial DNA (mtDNA). Interestingly, a connection between these entities has not been explored. Here we report that noradrenaline (NA) derived from the lung’s nerve supply drives accumulation of αSMA-expressing fibroblasts via mechanism involving α1 adrenoreceptors mtDNA. Using bleomycin model lung fibrosis compared effect specific denervation...