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Abstract
BACKGROUND Keratinocyte growth factor (KGF) stimulates gastrointestinal epithelial cells in vivo, and is protective against gastrointestinal injury and colitis. Endogenous KGF is increased in inflammatory bowel disease (IBD), and may be an important mediator of mucosal repair. KGF is expressed by mesenchymal cells and activated intraepithelial lymphocytes (IEL).
AIMS To investigate the relative contributions of these cellular sources of KGF expression in IBD.
METHODS IELs and lamina propria lymphocytes (LPL) were isolated from inflamed and uninflamed IBD tissues. mRNA expression was determined by ribonuclease protection assay. In situ hybridisation was combined with immunohistochemistry to determine whether KGF mRNA was expressed by specific cell types in vivo.
RESULTS Low levels of KGF mRNA expression were detected in three of five IEL samples derived from inflamed tissue, but not in two IEL samples from uninflamed tissue. No KGF expression was detected in LPLs from either inflamed or uninflamed tissue. In contrast, KGF was expressed by primary cultures of human intestinal fibroblasts, and was induced by treatment with interleukin 1.
CONCLUSIONS The major source of KGF expression in IBD was lamina propria cells of non-immune origin, most likely fibroblasts and/or smooth muscle cells. Compared with these cell types, relatively little KGF synthesis was associated with IELs in inflamed IBD tissue.
- fibroblasts
- intestinal inflammation
- intraepithelial lymphocytes
- keratinocyte growth factor
- lamina propria lymphocytes
Abbreviations used in this paper
- GAPDH
- glyceraldehyde 3-phosphate dehydrogenase
- HIF
- human intestinal fibroblasts
- IBD
- inflammatory bowel disease
- IEL
- intraepithelial lymphocytes
- IHC
- immunohistochemistry
- IL
- interleukin
- ISH
- in situ hybridisation
- KGF
- keratinocyte growth factor
- LPL
- lamina propria lymphocytes
- PCR
- polymerase chain reaction
- RPA
- ribonuclease protection assay