Activation of eosinophil CCR3 signaling and eotaxin using a bioinformatics analysis of a mouse model of obliterative airway disease.
The role of eosinophils in the development and progression of chronic allograft rejection is recognized in multiple organ transplantation settings. The CCR3 signaling pathway is one of the key regulatory pathways in eosinophil migration to the engrafted tissue. Eotaxin is a ligand for CCR3 and reflects eosinophilic inflammation, which can lead to fibrosis. We hypothesized that the CCR3 pathway would be upregulated in obliterative airway disease (OAD) in an established model of chronic airway allograft rejection. The mouse gene microarray data from a heterotopic mouse model of OAD in the NIH Gene Expression Omnibus (GEO) repository were analyzed for differentially expressed eosinophil pathways, using the Partek Suite and Ingenuity Pathway Analysis. A P value of <0.005 was defined as significant for differential expression, and P value of <0.05 for pathways. Day 25 allografts were defined as chronic allograft rejection and day 4 as acute allograft rejection. The isografts and allografts at day 25 showed significant upregulation of the eosinophil CCR3 pathway (P=0.04), based on the analysis of 1,299 uniquely expressed genes. The isografts at day 4 were compared with those at day 25 based on the identification of 1,859 unique genes, and there was a trend toward the CCR3 pathway upregulation over time (P=0.06). CCR3 pathways were not upregulated during the progression of alloimmune rejection in the allografts at day 4 versus day 25 in comparison, based on the analysis of 1,603 genes. Eotaxin was upregulated in chronic allograft rejection by 2.5-fold. The eosinophil signaling pathway CCR3 and eotaxin were significantly expressed in chronic allograft rejection and our results imply a role in controlling early alloimmune damage in controls.
The Department of Molecular and Experimental Medicine, The Scripps Research Institute , La Jolla, California.
Amrita
A
Dosanjh
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000235:genetics / Q000503:physiopathology*; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D004195:Disease Models, Animal; D015870:Gene Expression; D051379:Mice; D046228:Microarray Analysis; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D054413:Chemokine CCL11; D054397:Receptors, CCR3