Nicotinic α-7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU-282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL-1β, TNF-α, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P < 0.05). In addition, lung NF-κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase-9 and -2 cells, whereas the number of tissue inhibitor of metalloproteinase-1 cells increased (P < 0.05). PNU-282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2-related markers CD206 and IL-10 increased, suggesting changes in the macrophage profile. Finally, PNU-282987 improved lung function in LPS-treated animals. The collective results suggest that PNU-282987, an agonist of α7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.-Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Câmara, N. O. S., Wensing, L. A., Prado, V. F., Tibério, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1096/fj.201600431R | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anemonin suppresses sepsis-induced acute lung injury by inactivation of nuclear factor-kappa B and activation of nuclear factor erythroid 2-related factor-2/heme oxygenase-1 pathway.
FASEB J
January 2025
Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Sepsis-induced acute lung injury (ALI) is a common acute and severe reason of death in the intensive care unit. Although the pathogenesis is complicated and multifactorial, elevated inflammation and oxidative stress are considered as fundamental mechanisms for the progression of ALI. Anemonin is a natural compound with diverse biological properties including anti-inflammatory and anti-oxidative effects.
View Article and Find Full Text PDFSilencing of lncRNA Gm26917 Attenuates Alveolar Macrophage-mediated Inflammatory Response in LPS-induced Acute Lung Injury Via Inhibiting NKRF Ubiquitination.
Inflammation
January 2025
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China.
The inflammatory response mediated by alveolar macrophages plays a crucial role in the development of acute lung injury. Numerous studies have reported that lncRNAs are highly expressed in acute lung injury in mouse models and cell lines, and acute lung injury (ALI) can be effectively alleviated by targeting these lncRNAs. The aim of this study was to explore the mechanism by LncRNA Gm26917 regulates the inflammatory response in alveolar macrophages during acute lung injury mouse model.
View Article and Find Full Text PDFEstablishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections.
Adv Exp Med Biol
January 2025
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies.
View Article and Find Full Text PDFThe effect of a general practitioner's perception of a patient request for antibiotics on antibiotic prescribing for respiratory tract infections: secondary analysis of a point prevalence audit survey in 18 European countries.
BJGP Open
January 2025
Department of Family Medicine & Population Health, Belgium, University of Antwerp, Antwerp.
Background: Illness severity, comorbidity, fever, age and symptom duration influence antibiotic prescribing for respiratory tract infections (RTI). Non-medical determinants, such as patient expectations, also impact prescribing.
Aim: To quantify the effect of general practitioners' (GPs') perception of a patient request for antibiotics on antibiotic prescribing for RTI and investigate effect modification by medical determinants and country.
Extracellular peroxiredoxin 6 released from alveolar epithelial cells as a DAMP drives macrophage activation and inflammatory exacerbation in acute lung injury.
Int Immunopharmacol
January 2025
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China; Department of Pulmonary Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian 361015, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Respiratory Research Institute, Shanghai 200032, China.
Acute respiratory distress syndrome (ARDS) is featured with acute lung inflammatory injury. Our prospective study found that higher levels of peroxiredoxin 6(PRDX6) were detected in bronchoalveolar lavage (BAL) fluid from ARDS patients. Elevated PRDX6 was also correlated with monocytic activation and poor prognosis in ARDS patients.
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!