Inducible nitric oxide synthase (iNOS) and arginase-2 (ARG2) share a common substrate, arginine. Higher expression of iNOS and exhaled NO are linked to airway inflammation in patients. iNOS deletion in animal models suggests that eosinophilic inflammation is regulated by arginine metabolism. Moreover, ARG2 is a regulator of Th2 response, as shown by the development of severe eosinophilic inflammation in ARG2-/- mice. However, potential synergistic roles of iNOS and ARG2 in asthma have not been explored. Here, we hypothesized that arginine metabolic fate via iNOS and ARG2 may govern airway inflammation. In an asthma cohort, ARG2 variant genotypes were associated with arginase activity. ARG2 variants with lower arginase activity, combined with levels of exhaled NO, identified a severe asthma phenotype. Airway inflammation was present in WT, ARG2-/-, iNOS-/-, and ARG2-/-/iNOS-/- mice but was greatest in ARG2-/-. Eosinophilic and neutrophilic infiltration in the ARG2-/- mice was abrogated in ARG2-/-/iNOS-/- animals. Similarly, angiogenic airway remodeling was greatest in ARG2-/- mice. Cytokines driving inflammation and remodeling were highest in lungs of asthmatic ARG2-/- mice and lowest in the iNOS-/-. ARG2 metabolism of arginine suppresses inflammation, while iNOS metabolism promotes airway inflammation, supporting a central role for arginine metabolic control of inflammation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098726 | PMC |
| http://dx.doi.org/10.1172/jci.insight.127801 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sulfur dioxide exposure of mice induces peribronchiolar fibrosis-A defining feature of deployment-related constrictive bronchiolitis.
PLoS One
January 2025
Research Service and Pulmonary Section Medical Service, Veterans Affairs Ann Arbor Health System, Ann Arbor, Michigan, United States of America.
Deployment-related constrictive bronchiolitis (DRCB) has emerged as a health concern in military personnel returning from Southwest Asia. Exposure to smoke from a fire at the Al-Mishraq sulfur enrichment facility and/or burn pits was reported by a subset of Veterans diagnosed with this disorder. DRCB is characterized by thickening and fibrosis of small airways (SA) in the lung, but whether these are related to toxin inhalation remains uncertain.
View Article and Find Full Text PDFIron Drives Eosinophil Differentiation in Allergic Airway Inflammation Through Mitochondrial Metabolic Adaptation.
Adv Healthc Mater
January 2025
Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
Eosinophils play a crucial role as effector cells in asthma pathogenesis, with their differentiation being tightly regulated by metabolic mechanisms. While the involvement of iron in various cellular processes is well known, its specific role in eosinophil differentiation has largely remained unexplored. This study demonstrates that iron levels are increased during the differentiation process from eosinophil progenitors to mature and activated eosinophils in the context of allergic airway inflammation.
View Article and Find Full Text PDFEffect of miR-223-3p and miR-328a-3p Knockdown on Allergic Airway Inflammation in Rat Precision-Cut Lung Slices.
Cells
January 2025
Molecular and Cell Biology Unit, Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, 60-572 Poznan, Poland.
Asthma is a major non-communicable disease whose pathogenesis is still not fully elucidated. One of the asthma research models is precision-cut lung slices (PCLSs), and among the therapeutic options, miRNA molecules are of great interest. The aim of our study was to investigate whether inhibition of miR-223-3p and miR328a-3p affects the inflammatory response in PCLSs derived from a rat with HDM-induced allergic inflammation and a control rat.
View Article and Find Full Text PDFInhibitory Effects of Compounds Isolated from L. (Noni) Seeds against Particulate Matter-Induced Injury.
J Microbiol Biotechnol
December 2024
Institute of Agricultural Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea.
L. (noni) is native to the tropical and semitropical areas and has been commercially available in health food stores and chain grocery stores specializing in natural foods, recently. Noni seeds are discarded as waste products through the industrial production of noni juice even though their bioactivity components might be a potential source of functional foods.
View Article and Find Full Text PDFPassive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.
PLoS Pathog
January 2025
Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!