Molecular pathways altered by insulin b9-23 immunization.
Type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse can be delayed by administration of insulin or specific insulin peptides. To better understand how insulin treatment delays diabetes development, NOD mice treated with an insulin peptide (B9-23) were compared with age-matched NOD and NOD congenic mice for gene expression changes in spleen using cDNA microarray. Fifty genes were identified that were significantly altered by B9-23 treatment. Thirty-three of these genes are downregulated by the treatment while they are upregulated during the natural disease progression in NOD from immature (3-4 weeks) to mature (10 weeks) stages. Taken together, our data suggest that the B9-23 treatment, like the protective genes in NOD congenic strains, reduces pro-inflammatory activation of lymphocytes that normally occurs in NOD mice. Furthermore, our studies discovered two genes (Irf4 and Tra1) with increased expression in B9-23-treated mice that promote the Th2 response, providing a molecular basis for the B9-23-protective therapy.
Eckenrode
Sarah E
SE
CBGM, Medical College of Georgia, 1120 15th Street, CA-4124, Augusta, GA 30912, USA.
Ruan
Qing-Guo
QG
Collins
Christin D
CD
Yang
Ping
P
McIndoe
Richard A
RA
Muir
Andrew
A
She
Jin-Xiong
JX
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007114:Immunization; D007328:Insulin / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D007328:Insulin; D010446:Peptide Fragments