Interleukin-4 and interleukin-13 differentially regulate epithelial chloride secretion.
Intestinal epithelia are in intimate contact with subepithelial and intraepithelial lymphocytes. When stimulated, mucosal lymphocytes generate cytokines that act locally and influence functional aspects of many cell types. We have previously defined functional epithelial receptors for interferon-gamma, interleukin (IL)-4, and a recently described IL-4-like cytokine IL-13. In this study, we examine the ion transport properties of T84 cells, a crypt-like epithelial cell line, following exposure to IL-4 and IL-13. Basolateral exposure of epithelial monolayers to both IL-4 and IL-13 attenuated epithelial barrier function and increased paracellular flux of a dextran marker by greater than 65% in a dose- and time-dependent fashion. Stimulated Cl- secretion, as measured by epithelial short circuit current, however, was diminished only by IL-4 and not IL-13, demonstrating cytokine specificity in this epithelial function. Decreased Cl- secretion following IL-4 exposure was associated with diminished Cl- channel activity and IL-4 pretreatment of epithelia decreased expression of the cystic fibrosis transmembrane regulator. Finally, stimulated fluid transport across cultured epithelia was diminished following exposure to IL-4, but not IL-13. These results indicate that while post-receptor signaling events induced by IL-13 and IL-4 may be similar, end point function is cytokine-specific.
Zünd
G
G
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Madara
J L
JL
Dzus
A L
AL
Awtrey
C S
CS
Colgan
S P
SP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007422:Intestines; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
C505032:CFTR protein, human; D002712:Chlorides; D018793:Interleukin-13; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D015847:Interleukin-4; D007371:Interferon-gamma; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine