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Interleukin 2 modulates ion secretion and cell proliferation in cultured human small intestinal enterocytes
  1. E V O'Loughlina,
  2. G P Pangb,
  3. R Noltorpb,
  4. C Koinab,
  5. R Bateyb,
  6. R Clancyb
  1. aDepartment of Gastroenterology, Royal Alexandra Hospital for Children, Westmead, University of Newcastle, NSW, Australia, bFaculty of Medicine and Australian Institute of Mucosal Immunology, University of Newcastle, NSW, Australia
  1. Dr E O'Loughlin, Department of Gastroenterology, Royal Alexandra Hospital for Children, PO Box 3515, Parramatta 2124, NSW, Australia.tedo{at}nch.edu.au

Abstract

AIMS To determine if interleukin 2 (IL-2) alters epithelial transport and barrier function in cultured human small intestinal enterocytes.

METHODS Confluent monolayers of small intestinal cells derived from duodenal biopsies were treated with IL-2 0.2–50 U/ml for 24 hours prior to study. Transport measurements were performed under short circuited conditions in Ussing chambers, with and without the secretagogues forskolin and 3-isobutyl-1-methyl xanthine (IBMX). Serosal to mucosal flux of3[H] mannitol (permeability) and 3[H] thymidine uptake (proliferation) were measured. IL-2 receptor and cystic fibrosis transmembrane conductance regulator (CFTR) mRNA were identified using reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS IL-2 did not alter baseline electrical parameters but caused a significant increase in cAMP dependent chloride secretion. The effect was mediated by the IL-2 receptor and paralleled a rapid increase in tyrosine phosphorylation, janus kinase 1, and signal transducers and activators of transcription (STATs) 1, 3, and 5. IL-2 significantly increased proliferation but at a lower dose than observed for enhanced secretion but did not alter permeability. IL-2 receptor β and γc chains and CFTR mRNA were identified by RT-PCR.

CONCLUSIONS IL-2 treatment enhances cAMP stimulated chloride secretion and cellular proliferation in a human small intestinal cell line expressing a functional IL-2 receptor.

  • interleukin 2
  • ion secretion
  • cell proliferation
  • enterocytes
  • small intestine

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