RGD Reference Report - Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke.

Authors: Rajendrasozhan, S  Hwang, JW  Yao, H  Kishore, N  Rahman, I 
Citation: Rajendrasozhan S, etal., Pulm Pharmacol Ther. 2010 Jun;23(3):172-81. doi: 10.1016/j.pupt.2010.01.002. Epub 2010 Jan 18.
RGD ID: 7495767
Pubmed: PMID:20080200   (View Abstract at PubMed)
PMCID: PMC2850968   (View Article at PubMed Central)
DOI: DOI:10.1016/j.pupt.2010.01.002   (Journal Full-text)

RATIONALE: IkappaB 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-di hydro-1H-benzo[gamma]indazole-3-carboxamide], in lungs of rat in vivo. METHODS: Adult 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. RESULTS: Oral 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. CONCLUSION: These results suggest that IKKbeta/IKK2 inhibitor PHA-408 is a powerful anti-inflammatory agent against LPS- and CS-mediated lung inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pneumonia treatmentISOIkbkb (Rattus norvegicus)7495767; 7495767 RGD 
pneumonia treatmentIMP 7495767 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ikbkb  (inhibitor of nuclear factor kappa B kinase subunit beta)

Genes (Mus musculus)
Ikbkb  (inhibitor of kappaB kinase beta)

Genes (Homo sapiens)
IKBKB  (inhibitor of nuclear factor kappa B kinase subunit beta)


Additional Information