Synergistic effect of IL-4 and IFN-gamma on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells.
The expression of secretory component (SC), the epithelial receptor for polymeric Ig, was enhanced by the addition of human rIFN-gamma or rIL-4, as revealed by the binding of radiolabeled polymeric, J chain-containing IgA or anti-SC antisera to the human colonic adenocarcinoma epithelial cell line HT-29. In combination, these cytokines exhibited a synergistic effect, and the potentiating effect of IL-4 was inhibitable by polyclonal anti-IL-4 antisera. Because the binding of radiolabeled polymeric IgA (pIgA) to HT-29 cells was inhibited by unlabeled pIgA or a polyclonal anti-SC reagent, but not by IgG, monomeric IgA, or Fab alpha fragments, we conclude that the receptor involved in the increased binding of pIgA is indeed SC. These data suggest that the expression of SC on human epithelial cells and the subsequent binding of pIgA (produced in mucosal tissues and glands by subepithelial plasma cells) is regulated by lymphokines such as IL-4 and IFN-gamma that are presumably derived from T cells found in abundant numbers in these tissues. These findings demonstrate a novel pathway of interaction between T cell products and epithelial cells that may result in enhanced translocation of large amounts of locally produced pIgA through epithelial cells into external secretions.
Phillips
J O
JO
Department of Microbiology, University of Alabama, Birmingham 35294.
Everson
M P
MP
Moldoveanu
Z
Z
Lue
C
C
Mestecky
J
J
D001685:Biological Factors / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines; D004848:Epithelium / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D007158:Immunologic Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D012635:Secretory Component / Q000378:metabolism*
D001685:Biological Factors; D016207:Cytokines; D007070:Immunoglobulin A; D007128:Immunoglobulin Fragments; D007378:Interleukins; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D012635:Secretory Component; C034639:polymeric IgA; D015847:Interleukin-4; D007371:Interferon-gamma