Interleukin 2 modulates intestinal epithelial cell function in vitro

被引:70
作者
Dignass, AU
Podolsky, DK
机构
[1] MASSACHUSETTS GEN HOSP,GASTROENTEROL UNIT,DEPT MED,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02114
关键词
D O I
10.1006/excr.1996.0193
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although interleukin 2 (IL-2) has been presumed to have a highly circumscribed range of target cells limited largely to classic immune cell populations, the presence of functional IL-2 receptors in rat epithelial cell lines has recently been demonstrated. Limited information is available about the functional effects of IL-2 on intestinal epithelial cells. The effect of recombinant IL-2 on intestinal epithelial cell migration was assessed using a previously described in vitro model of epithelial restitution by quantitation of cells migrating into standard wounds established in confluent IEC-B cell monolayers, Transforming growth factor beta content was assessed by Northern blot and bioassay. Exogenous IL-2 enhanced epithelial cell restitution in vitro on average 3.8-fold; this effect was independent of cell proliferation. Enhancement of restitution through IL-2 could be completely blocked through antibodies directed against TGF beta(1) and interleukin-2 receptor, indicating that stimulation of epithelial cell restitution is specifically enhanced by interleukin-2 and mediated through a TGF beta-dependent pathway. In addition, increased expression of TGF beta(1) mRNA and increased levels of bioactive TGF beta peptide in wounded monolayers treated with IL-2 compared to unwounded monolayers cultured in serum-deprived medium alone support the notion that enhancement of epithelial cell restitution in vitro is mediated through a TGF beta-dependent pathway. These studies suggest that IL-2, a potent cytokine whose biological origin and targets have been presumed to be largely limited to lymphocyte and macrophage populations, may play a role in preserving the integrity of the intestinal epithelium following various forms of injuries. (C) 1996 Academic Press, Inc.
引用
收藏
页码:422 / 429
页数:8
相关论文
共 44 条
  • [1] REGULATION OF INTESTINAL EPITHELIAL-CELL GROWTH BY TRANSFORMING GROWTH-FACTOR TYPE-BETA
    BARNARD, JA
    BEAUCHAMP, RD
    COFFEY, RJ
    MOSES, HL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (05) : 1578 - 1582
  • [2] EXPRESSION OF MURINE CD1 ON GASTROINTESTINAL EPITHELIUM
    BLEICHER, PA
    BALK, SP
    HAGEN, SJ
    BLUMBERG, RS
    FLOTTE, TJ
    TERHORST, C
    [J]. SCIENCE, 1990, 250 (4981) : 679 - 682
  • [3] Blumberg R S, 1994, Int Rev Immunol, V11, P15, DOI 10.3109/08830189409061714
  • [4] INTERLEUKIN-1 AND INTERLEUKIN-3 STIMULATE ANION SECRETION IN CHICKEN INTESTINE
    CHANG, EB
    MUSCH, MW
    MAYER, L
    [J]. GASTROENTEROLOGY, 1990, 98 (06) : 1518 - 1524
  • [5] CHIRGWIN JM, 1979, BIOCHEMISTRY-US, V18, P5295
  • [6] FUNCTIONAL INTERLEUKIN-2 RECEPTORS ON INTESTINAL EPITHELIAL-CELLS
    CIACCI, C
    MAHIDA, YR
    DIGNASS, A
    KOIZUMI, M
    PODOLSKY, DK
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (01) : 527 - 532
  • [7] TRANSFORMING GROWTH-FACTOR-BETA REGULATION OF MIGRATION IN WOUNDED RAT INTESTINAL EPITHELIAL MONOLAYERS
    CIACCI, C
    LIND, SE
    PODOLSKY, DK
    [J]. GASTROENTEROLOGY, 1993, 105 (01) : 93 - 101
  • [8] COFFEY RJ, 1987, CANCER RES, V47, P4590
  • [9] TREFOIL PEPTIDES PROMOTE EPITHELIAL MIGRATION THROUGH A TRANSFORMING GROWTH-FACTOR BETA-INDEPENDENT PATHWAY
    DIGNASS, A
    LYNCHDEVANEY, K
    KINDON, H
    THIM, L
    PODOLSKY, DK
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (01) : 376 - 383
  • [10] HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR MODULATES INTESTINAL EPITHELIAL-CELL PROLIFERATION AND MIGRATION
    DIGNASS, AU
    LYNCHDEVANEY, K
    PODOLSKY, DK
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 202 (02) : 701 - 709