Pharmacogenomic analysis of rhIL-11 treatment in the HLA-B27 rat model of inflammatory bowel disease.
Recombinant human interleukin-11 (rhIL-11) reduces the clinical signs and histological lesions of inflammatory bowel disease (IBD) in transgenic rats expressing the human major histocompatability complex (MHC) class I allele, HLA-B27. To elucidate the pharmacogenomic effects of rhIL-11 in this model, we examined the global gene expression pattern in inflamed colonic tissue before and following rhIL-11 treatment using oligonucleotide microarrays. In total, 175 disease-related genes were identified. Increased expression of genes involved in antigen presentation, cell death and inflammation, and decreased expression of metabolic genes was associated with disease. A total of 27 disease-related genes returned to normal expression levels following rhIL-11 treatment including the MHC class II gene RT1-DMbeta. rhIL-11 induced the expression of four intestinal epithelial growth factors. These gene expression patterns indicate that treatment of inflammatory bowel disease with rhIL-11 affects class II antigen processing and colonic epithelial cell proliferation and metabolism.
Peterson
R L
RL
Department of Molecular Medicine and Pharmacogenomics, 1 Burtt Road, Andover, MA, USA. rpeterson@wyeth.com
Wang
L
L
Albert
L
L
Marchese
E
E
Erickson
J
J
Wong
A
A
Mounts
W M
WM
Hayes
L
L
Bouchard
P
P
Keith
J
J
Dorner
A J
AJ
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015796:HLA-B27 Antigen / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics; D017370:Interleukin-11 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010597:Pharmacogenetics / Q000379:methods* / Q000706:statistics & numerical data; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*
D015796:HLA-B27 Antigen; D017370:Interleukin-11; D011994:Recombinant Proteins; C105308:oprelvekin