Insulinlike growth factor I and interleukin 1 beta messenger RNA in a rat model of granulomatous enterocolitis and hepatitis.
BACKGROUND
Insulinlike growth factor I (IGF-I) is mitogenic for fibroblasts and smooth muscle cells and stimulates collagen synthesis. The present study tested the hypothesis that IGF-I is important in the development of granulomatous inflammation and fibrosis.


METHODS
IGF-I messenger RNA (mRNA) was measured in bowel and liver of rats with peptidoglycan-polysaccharide-induced chronic granulomatous enterocolitis and hepatitis using RNase protection. Cellular sites of IGF-I mRNA and IGF-I peptide precursor were localized by in situ hybridization and immunohistochemistry, respectively. Sites of IGF-I synthesis were compared with sites of interleukin 1 beta mRNA expression.


RESULTS
IGF-I mRNA was increased 3.7-fold in cecal tissue from peptidoglycan-polysaccharide-injected rats compared with controls. IGF-I mRNA was up-regulated in fibroblastlike cells in the intensely fibrotic periphery of cecal and hepatic granulomas. This region also expressed IGF-I peptide precursor. Interleukin 1 mRNA localized to macrophage-like cells in the center of granulomas.


CONCLUSIONS
IGF-I may be important in the development of fibrosis in this model of Crohn's disease. The localization of IGF-I and interleukin 1 mRNAs to distinct but adjacent sites is consistent with a paracrine interaction between cells expressing IGF-I and interleukin 1.
Zimmermann
E M
EM
Department of Internal Medicine, University of Michigan, Ann Arbor.
Sartor
R B
RB
McCall
R D
RD
Pardo
M
M
Bender
D
D
Lund
P K
PK
D000818:Animals; D002432:Cecum / Q000378:metabolism; D004760:Enterocolitis / Q000378:metabolism*; D005260:Female; D006099:Granuloma / Q000378:metabolism*; D006520:Hepatitis, Animal / Q000378:metabolism*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
D007375:Interleukin-1; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I