Article
Keratinocyte growth factor and coeliac
disease
V M Salvatia, M Bajaj-Elliottb, R Poulsomc, G Mazzarellad, K E A Lundine, E M Nilsenf, R Tronconea, T T MacDonaldg
a Department
of Paediatrics and European Laboratory for the Investigation of
Food-Induced Diseases, University Federico II, Naples, Italy, b Department of Adult
and Paediatric Gastroenterology, St Bartholomew's and the Royal London
School of Medicine and Dentistry, London, UK, c Histopathology Unit, Imperial Cancer Research
Fund, London, UK, d Institute
of Food, Science, and Technology, CNR Avellino, Italy, e Institute of Immunology, The National
Hospital, University of Oslo, Norway, f LIIPAT Institute of Pathology, The National
Hospital, University of Oslo, Norway, g Division of Infection, Inflammation, and Repair,
University of Southampton, School of Medicine, Southampton, UK
Correspondence to: T T MacDonald, Division of Infection, Inflammation, and Repair, School of Medicine, Southampton General Hospital, MailPoint 813, Level E, South Academic Block, Tremona Road, Southampton SO16 6YD, UK. t.t.macdonald{at}soton.ac.uk
Accepted for publication 26 February 2001
BACKGROUND
Coeliac
disease is characterised by increased epithelial renewal associated
with a mucosal T cell response to gliadin. Keratinocyte growth factor
(KGF) is produced by cytokine activated gut stromal cells and may be a
link between mucosal T cell activation in untreated coeliac disease and
epithelial hyperplasia.
AIMSTo characterise
expression of KGF in coeliac disease.
METHODSKGF
transcripts in coeliac disease were measured by quantitative
competitive reverse transcription-polymerase chain reaction (RT-PCR)
and localised using in situ hybridisation. KGF production by gluten
reactive CD4+ T cell clones was examined. In addition, KGF transcripts
were measured following ex vivo challenge of coeliac biopsies with a
peptic-tryptic digest of gliadin.
RESULTSKGF
transcripts were elevated in coeliac biopsies compared with normal
controls but were not different from non-coeliac disease controls. By
in situ hybridisation, KGF mRNA containing cells were present in the
upper half of the lamina propria, most abundantly just under the
epithelium. There was no signal from cells within the epithelium.
Gluten reactive T cell clones did not make KGF. In vitro challenge of
coeliac biopsies generated a strong interferon 
response but a
specific KGF response could not be detected because of an extremely
high number of KGF transcripts in all cultured biopsies.
CONCLUSIONSKGF is
overexpressed in coeliac biopsies and in tissues with non-coeliac
enteropathy. No evidence was found for KGF production by
intraepithelial lymphocytes or lamina propria T cells.
Keywords: coeliac disease; keratinocyte growth factor; mRNA expression
© 2001 by Gut
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