RGD Reference Report - Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs. - 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 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
Advanced Search (OLGA)

Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs.

Authors: Makam, M  Diaz, D  Laval, J  Gernez, Y  Conrad, CK  Dunn, CE  Davies, ZA  Moss, RB  Herzenberg, LA 
Citation: Makam M, etal., Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5779-83. Epub 2009 Mar 17.
RGD ID: 5133738
Pubmed: PMID:19293384   (View Abstract at PubMed)
PMCID: PMC2667067   (View Article at PubMed Central)

Cystic fibrosis (CF) patients undergo progressive airway destruction caused in part by chronic neutrophilic inflammation. While opportunistic pathogens infecting CF airways can cause inflammation, we hypothesized that host-derived metabolic and stress signals would also play a role in this process. We show that neutrophils that have entered CF airways have increased phosphorylation of the eukaryotic initiation factor 4E and its partner the 4E-binding protein 1; 2 key effectors in the growth factor- and amino acid-regulated mammalian target of rapamycin (mTOR) pathway. Furthermore CF airway neutrophils display increased phosphorylation of the cAMP response element binding protein (CREB), a major transcriptional coactivator in stress signaling cascades. These active intracellular pathways are associated with increased surface expression of critical adaptor molecules, including the growth factor receptor CD114 and the receptor for advanced glycation end-products (RAGE), a CREB inducer and sensor for host-derived damage-associated molecular patterns (DAMPs). Most CF airway fluids lack any detectable soluble RAGE, an inhibitory decoy receptor for DAMPs. Concomitantly, CF airway fluids displayed high and consequently unopposed levels of S100A12; a potent mucosa- and neutrophil-derived DAMP. CF airway neutrophils also show increased surface levels of 2 critical CREB targets, the purine-recycling enzyme CD39 and the multifunctional, mTOR-inducing CXCR4 receptor. This coordinated set of events occurs in all patients, even in the context of minimal airway inflammation and well-preserved lung function. Taken together, our data demonstrate an early and sustained activation of host-responsive metabolic and stress pathways upon neutrophil entry into CF airways, suggesting potential targets for therapeutic modulation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CSF3RHumancystic fibrosis  IEP protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 
Csf3rRatcystic fibrosis  ISOCSF3R (Homo sapiens)protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 
Csf3rMousecystic fibrosis  ISOCSF3R (Homo sapiens)protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 

Objects Annotated

Genes (Rattus norvegicus)
Csf3r  (colony stimulating factor 3 receptor)

Genes (Mus musculus)
Csf3r  (colony stimulating factor 3 receptor)

Genes (Homo sapiens)
CSF3R  (colony stimulating factor 3 receptor)

Objects referenced in this article
Gene CSF3 colony stimulating factor 3 Homo sapiens

Additional Information