RGD Reference Report - MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. - 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

MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.

Authors: Salcedo, Rosalba  Worschech, Andrea  Cardone, Marco  Jones, Yava  Gyulai, Zsofia  Dai, Ren-Ming  Wang, Ena  Ma, Winnie  Haines, Diana  O'hUigin, Colm  Marincola, Francesco M  Trinchieri, Giorgio 
Citation: Salcedo R, etal., J Exp Med. 2010 Aug 2;207(8):1625-36. doi: 10.1084/jem.20100199. Epub 2010 Jul 12.
RGD ID: 150520020
Pubmed: PMID:20624890   (View Abstract at PubMed)
PMCID: PMC2916129   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20100199   (Journal Full-text)

Signaling through the adaptor protein myeloid differentiation factor 88 (MyD88) promotes carcinogenesis in several cancer models. In contrast, MyD88 signaling has a protective role in the development of azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-associated cancer (CAC). The inability of Myd88(-/-) mice to heal ulcers generated upon injury creates an altered inflammatory environment that induces early alterations in expression of genes encoding proinflammatory factors, as well as pathways regulating cell proliferation, apoptosis, and DNA repair, resulting in a dramatic increase in adenoma formation and progression to infiltrating adenocarcinomas with frequent clonal mutations in the beta-catenin gene. Others have reported that toll-like receptor (Tlr) 4-deficient mice have a similar susceptibility to colitis to Myd88-deficient mice but, unlike the latter, are resistant to CAC. We have observed that mice deficient for Tlr2 or Il1r do not show a differential susceptibility to colitis or CAC. However, upon AOM/DSS treatment Il18(-/-) and Il18r1(-/-) mice were more susceptible to colitis and polyp formation than wild-type mice, suggesting that the phenotype of Myd88(-/-) mice is, in part, a result of their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that impact tissue homeostasis and carcinogenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MYD88HumanColonic Polyps  ISOMyd88 (Mus musculus) RGD 
Myd88RatColonic Polyps  ISOMyd88 (Mus musculus) RGD 
Myd88MouseColonic Polyps  IMP  RGD 
MYD88Humandiarrhea  ISOMyd88 (Mus musculus) RGD 
Myd88Ratdiarrhea  ISOMyd88 (Mus musculus) RGD 
Myd88Mousediarrhea  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myd88  (MYD88, innate immune signal transduction adaptor)

Genes (Mus musculus)
Myd88  (myeloid differentiation primary response gene 88)

Genes (Homo sapiens)
MYD88  (MYD88 innate immune signal transduction adaptor)


Additional Information