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Analysis of the cellular basis of keratinocyte growth factor overexpression in inflammatory bowel disease
  1. P W Finch,
  2. A L Cheng
  1. Derald H. Ruttenberg Cancer Centre, Mount Sinai School of Medicine, New York, USA
  1. Dr P W Finch, The Derald H. Ruttenberg Cancer Centre, Box 1130, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029–6574, USA.

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

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Footnotes

  • 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

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