Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia--reperfusion injury and inflammation. The aim of the present study was to evaluate the effects of a novel and potent inhibitor of PARP activity on neutrophil recruitment in the acute inflammation induced by zymosan-activated plasma. Intra-thoracic administration of zymosan-activated plasma leads to an increase in neutrophil infiltration of the lung at 24hr. The potent PARP inhibitor 5-aminoisoquinolinone (5-AIQ) reduced the degree of lung injury and attenuated the expression of P-selectin and ICAM-1 as well as the recruitment of neutrophils into the injured lung. The up-regulation/expression of P-selectin and ICAM-1 in human endothelial cells exposed to oxidative stress (peroxynitrite) or to a pro-inflammatory cytokine (tumor necrosis factor alpha, TNFalpha) was also attenuated by 5-AIQ. These findings provide the first evidence that the activation of PARS participates in neutrophil-mediated lung injury by regulating the expression of P-selectin and ICAM-1.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0006-2952(01)00864-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role of inflammasomes in acute respiratory distress syndrome.
Thorax
January 2025
Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK.
Acute respiratory distress syndrome (ARDS) is present in >10% of all people admitted to critical care and is associated with severe morbidity and mortality. Despite more than half a century since its first description, no efficacious pharmacological therapies have been developed, and little progress has been made in improving clinical outcomes. Neutrophils are the principal drivers of ARDS, with their priming and subsequent aberrant downstream functions, including interleukin (IL) 1β and IL-18 secretion, central to the disease pathogenesis.
View Article and Find Full Text PDFLetermovir should be first-line cytomegalovirus prophylaxis in lung transplant recipients.
Am J Transplant
January 2025
Division of Pulmonary and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA.
Universal cytomegalovirus (CMV) prophylaxis is recommended for at-risk lung transplant recipients. Valganciclovir is currently the preferred first-line agent. Valganciclovir-related myelosuppression, however, can lead to drug discontinuation or reduction in anti-metabolite immunosuppression.
View Article and Find Full Text PDFDamage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection.
Mucosal Immunol
January 2025
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh Medical Center Pittsburgh PA USA; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine New Haven CT USA. Electronic address:
Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood.
View Article and Find Full Text PDFCombating sepsis-induced acute lung injury: PARP1 inhibition mediates oxidative stress mitigation and miR-135a-5p/SMAD5/Nanog axis drives regeneration.
Int Immunopharmacol
January 2025
Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India. Electronic address:
Purpose: The purpose of this study was to investigate the therapeutic potential of Poly (ADP-ribose) polymerase 1 (PARP1) inhibition combined with microRNA miR-135a-5p overexpression in sepsis-induced acute lung injury (ALI). Specifically, we aimed to elucidate combinatorial therapeutic potential of PARP1 inhibition in mitigating oxidative stress and inflammation across different models, simultaneously miR-135a-5p overexpression promoting regeneration through the SMAD5/Nanog axis.
Method: We used C57BL/6 mice to create Cecal Ligation Puncture (CLP) model of Sepsis-induced Acute Lung Injury.
Hesperetin alleviates PM2.5-induced lung injury by inhibiting ferroptosis in an Nrf2-dependent manner.
Int Immunopharmacol
January 2025
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021 China. Electronic address:
Background: Fine particulate matter (PM2.5) is a global environmental problem that threatens public health because it can induce ferroptosis and cause lung injury. Hesperetin (Hes), a natural compound widely present in fruits and vegetables, can activate nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting powerful antioxidant effects.
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!