| Involvement of eotaxin, eosinophils, and pancreatic predisposition in development of type 1 diabetes mellitus in the BioBreeding rat. | |
| | |
MedLine Citation:
|
PMID: 15557196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Allergy and autoimmunity are both examples of deregulated immunity characterized by inflammation and injury of targeted tissues that have until recently been considered disparate disease processes. However, recent findings have implicated mast cells, in coordination with granulocytes and other immune effector cells, in the pathology of these two disorders. The BioBreeding (BB) DRlyp/lyp rat develops an autoimmune insulin-dependent diabetes similar to human type 1 diabetes mellitus (T1DM), whereas the BBDR+/+ rat does not. To better understand immune processes during development of T1DM, gene expression profiling at day (d) 40 (before insulitis) and d65 (before disease onset) was conducted on pancreatic lymph nodes of DRlyp/lyp, DR+/+, and Wistar-Furth (WF) rats. The eosinophil-recruiting chemokine, eotaxin, and the high-affinity IgE receptor (FcepsilonRI) were up-regulated >5-fold in d65 DRlyp/lyp vs d65 DR+/+ pancreatic lymph nodes by microarray (p < 0.05) and quantitative RT-PCR studies (p < 0.05). DR+/+, WF, and d40 DRlyp/lyp animals possessed normal pancreatic histology; however, d65 DRlyp/lyp animals possessed eosinophilic insulitis. Therefore, immunohistochemistry for pancreatic eotaxin expression was conducted, revealing positive staining of d65 DRlyp/lyp islets. Islets of d65 DR+/+ rats also stained positively, consistent with underlying diabetic predisposition in the BB lineage, whereas WF islets did not. Other differentially expressed transcripts included those associated with eosinophils, mast cells, and lymphocytes. These data support an important role for these inflammatory mediators in BB rat T1DM and suggest that the lymphopenia due to the Ian5/(lyp) mutation may result in a deregulation of cells involved in insulitis and beta cell destruction. |
| | |
Authors:
|
Martin J Hessner; Xujing Wang; Lisa Meyer; Rhonda Geoffrey; Shuang Jia; Jessica Fuller; Ake Lernmark; Soumitra Ghosh |
Related Documents
:
|
17130556 - Normal t cell development in the absence of thymic insulin expression. 7604176 - Pravastatin-associated myopathy. report of a case. 11272136 - Prolonged islet graft survival in nod mice by blockade of the cd40-cd154 pathway of t-c... 16623756 - Development of diabetes in non-obese diabetic mice promotes chlamydia pneumoniae dissem... 20150296 - Moisture status of the skin of the feet assessed by the visual test neuropad correlates... 7525206 - Uptake and toxicological effects of some heavy metals on pleurotus sajor-caju (fr.) sin... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 173 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2004 Dec |
Date Detail:
|
Created Date: 2004-11-23 Completed Date: 2005-01-14 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 6993-7002 Citation Subset: AIM; IM |
Affiliation:
|
The Max McGee National Research Center for Juvenile Diabetes, Department of Pediatrics at the Medical College of Wisconsin and the Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA. mhessner@mcw.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Movement / genetics, immunology Chemokine CCL11 Chemokines, CC / biosynthesis, genetics, physiology* Diabetes Mellitus, Type 1 / genetics, immunology*, pathology Eosinophils / pathology* Gene Expression Profiling Genetic Predisposition to Disease* Immunohistochemistry Islets of Langerhans / immunology, pathology Lymph Nodes / chemistry, immunology, pathology Mast Cells / immunology, pathology Oligonucleotide Array Sequence Analysis Pancreas / immunology*, pathology Prediabetic State / genetics, immunology*, pathology Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatase, Non-Receptor Type 22 Protein Tyrosine Phosphatases / biosynthesis, genetics Rats Rats, Inbred BB* Rats, Inbred WF Receptors, IgE / biosynthesis, genetics Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
|
EB001421/EB/NIBIB NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/CCL11 protein, human; 0/Ccl11 protein, rat; 0/Chemokine CCL11; 0/Chemokines, CC; 0/Receptors, IgE; EC 3.1.3.48/PTPN22 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 1; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 22; EC 3.1.3.48/Protein Tyrosine Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis.
Next Document: NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness.