ArticlePulmonary pharmacology & therapeutics2010
Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke.
Article in Pulmonary pharmacology & therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Pulmonary Emphysema: Current Understanding of Disease Pathogenesis and Therapeutic Approaches.Biomedicines · 2025Review
- FNF-12, a novel benzylidene-chromanone derivative, attenuates inflammatory response in in vitro and in vivo asthma models mediated by M2-related Th2 cytokines via MAPK and NF-kB signaling.Pharmacological reports : PR · 2022Article
- Glycyl-L-histidyl-L-lysine-CuFrontiers in molecular biosciences · 2022Article
- Advances in Immunosuppressive Agents Based on Signal Pathway.Frontiers in pharmacology · 2022Review
- Progress in the mechanism and targeted drug therapy for COPD.Signal transduction and targeted therapy · 2020Review
- Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF-κB Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice.Inflammation · 2018Article
- Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors.Cells · 2018Review
- The Isosteroid Alkaloid Imperialine from Bulbs of Fritillaria cirrhosa Mitigates Pulmonary Functional and Structural Impairment and Suppresses Inflammatory Response in a COPD-Like Rat Model.Mediators of inflammation · 2016Article
- Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2015Article
- NF-kappaB Signaling in Chronic Inflammatory Airway Disease.Biomolecules · 2015Review
- Oxidants induce a corticosteroid-insensitive phosphorylation of histone 3 at serine 10 in monocytes.PloS one · 2015Article
- Lead Screening for Chronic Obstructive Pulmonary Disease of IKK2 Inhibited by Traditional Chinese Medicine.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- Berberine attenuates cigarette smoke-induced acute lung inflammation.Inflammation · 2013Article
- Article
- Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects.British journal of clinical pharmacology · 2012Article
- p38 MAPK inhibitors, IKK2 inhibitors, and TNFα inhibitors in COPD.Current opinion in pharmacology · 2012Review
- SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice.The Journal of clinical investigation · 2012Article
- Rat airway morphometry measured from in situ MRI-based geometric models.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Article
- Article
- Lung-targeted overexpression of the NF-κB member RelB inhibits cigarette smoke-induced inflammation.The American journal of pathology · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleIkappaB kinase (IKK) activates NF-kappaB which plays a pivotal role in pro-inflammatory response in the lung. NF-kappaB has been shown to be activated in alveolar macrophages and peripheral lungs of smokers and patients with chronic obstructive pulmonary disease. We investigated the anti-inflammatory effect of a highly selective and novel IKKbeta/IKK2 inhibitor, PHA-408 [8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[gamma]indazole-3-carboxamide], in lungs of rat in vivo.
methodsAdult Sprague-Dawley rats were administered orally with PHA-408 (15 and 45 mg/kg) daily for 3 days and exposed to LPS aerosol (once on day 3, 2 h post-last PHA-408 administration) or cigarette smoke (CS; 2h after PHA-408 administration for 3 days). Animals were sacrificed at 1, 4 and 24 h after the last exposure, and lung inflammatory response and NF-kappaB activation were measured.
resultsOral administration of IKKbeta/IKK2 inhibitor PHA-408 significantly inhibited LPS- and CS-mediated neutrophil influx in bronchoalveolar lavage (BAL) fluid of rats. The levels of pro-inflammatory mediators in BAL fluid (CINC-1) and lungs (IL-6, TNF-alpha, IL-1beta and GM-CSF) were also reduced by PHA-408 administration in response to LPS or CS exposures. The reduced pro-inflammatory response in PHA-408-administered rats was associated with decreased nuclear translocation and DNA binding activity of NF-kappaB in response to LPS or CS.
conclusionThese results suggest that IKKbeta/IKK2 inhibitor PHA-408 is a powerful anti-inflammatory agent against LPS- and CS-mediated lung inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.