RGD Reference Report - IL-27/IFN-gamma induce MyD88-dependent steroid-resistant airway hyperresponsiveness by inhibiting glucocorticoid signaling in macrophages. - 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

IL-27/IFN-gamma induce MyD88-dependent steroid-resistant airway hyperresponsiveness by inhibiting glucocorticoid signaling in macrophages.

Authors: Li, JJ  Wang, W  Baines, KJ  Bowden, NA  Hansbro, PM  Gibson, PG  Kumar, RK  Foster, PS  Yang, M 
Citation: Li JJ, etal., J Immunol. 2010 Oct 1;185(7):4401-9. Epub 2010 Sep 3.
RGD ID: 4145651
Pubmed: PMID:20817868   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1001039   (Journal Full-text)

Inflammation and airway hyperresponsiveness (AHR) are hallmark features of asthma and often correlate with the severity of clinical disease. Although these features of asthma can be effectively managed with glucocorticoid therapy, a subgroup of patients, typically with severe asthma, remains refractory to therapy. The mechanisms leading to steroid resistance in severe asthmatics are poorly understood but may be related to the activation of innate host defense pathways. Previously, we have shown that IFN-gamma-producing cells and LPS, two factors that are associated with severe asthma, induce steroid-resistant AHR in a mouse model. We now demonstrate that cooperative signaling induced by IFN-gamma and LPS results in the production of IL-27 by mouse pulmonary macrophages. IL-27 and IFN-gamma uniquely cooperate to induce glucocorticoid-resistant AHR through a previously unknown MyD88-dependent mechanism in pulmonary macrophages. Importantly, integrated signaling by IL-27/IFN-gamma inhibits glucocorticoid-induced translocation of the glucocorticoid receptor to the nucleus of macrophages. Furthermore, expression of both IL-27 and IFN-gamma was increased in the induced sputum of steroid-refractory asthmatics. These results suggest that a potential mechanism for steroid resistance in asthma is the activation of MyD88-dependent pathways in macrophages that are triggered by IL-27 and IFN-gamma, and that manipulation of these pathways may be a therapeutic target.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IEP 4145651; 4145651protein:increased expression:sputumRGD 
asthma  ISOIFNG (Homo sapiens)4145651; 4145651protein:increased expression:sputumRGD 
asthma  ISOIL27 (Homo sapiens)4145651; 4145651protein:increased expression:sputumRGD 
respiratory allergy  ISOIl27 (Mus musculus)4145651; 4145651 RGD 
respiratory allergy  IMP 4145651 RGD 
status asthmaticus resistanceISOIfng (Mus musculus)4145651; 4145651 RGD 
status asthmaticus resistanceIDA 4145651 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifng  (interferon gamma)
Il27  (interleukin 27)

Genes (Mus musculus)
Ifng  (interferon gamma)
Il27  (interleukin 27)

Genes (Homo sapiens)
IFNG  (interferon gamma)
IL27  (interleukin 27)


Additional Information