Interleukin 2 modulates ion secretion and cell proliferation in cultured human small intestinal enterocytes.
OBJECTIVE
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 of 3[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 beta and gammac 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.
O'Loughlin
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EV
Department of Gastroenterology, Royal Alexandra Hospital for Children, Westmead, University of Newcastle, NSW, Australia. tedo@nch.edu.au
Pang
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GP
Noltorp
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R
Koina
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Batey
R
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Clancy
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R
D000704:Analysis of Variance; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects; D018118:Chloride Channels / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008353:Mannitol / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D019820:Xanthine / Q000494:pharmacology
C505032:CFTR protein, human; D018118:Chloride Channels; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019820:Xanthine; D005576:Colforsin; D008353:Mannitol; D000242:Cyclic AMP; D013936:Thymidine