TY - JOUR
T1 - Alteration of gene expression by intestinal epithelial cells precedes colitis in interleukin-2-deficient mice
AU - Meijssen, Maarten A C
AU - Brandwein, Steven L.
AU - Reinecker, Hans Christian
AU - Bhan, Atul K.
AU - Podolsky, Daniel K.
PY - 1998/3
Y1 - 1998/3
N2 - Intestinal epithelial cells may be actively involved in the immunoregulatory pathways leading to intestinal inflammation. The aim of this study was to assess expression by intestinal epithelial cells of cytokines with potential involvement in the development of intestinal inflammation in interleukin (IL)-2-deficient [(-/-)] mice. Wild-type mice, mice heterozygous for the disrupted IL-2 gene, and IL-2(-/-) mice were studied at 6, 16, and 24 wk of age. The mRNA levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), IL-1β, IL-6, IL-15, KC, JE, and CD14 in colonic and small intestinal epithelial cells were assessed by Northern blot analysis. CD14 was also measured by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). TGF-β1 mRNA was constitutively expressed in both colonic and small intestinal epithelial cells with increased expression in the colonic epithelium of colitic mice. CD14 was detected only in colonic epithelial cells, and mRNA levels increased severalfold in IL-2(-/-) mice with colitis. Northern analysis demonstrated increased levels of TGF-β1 and CD14 mRNA in colonic epithelial cells of IL- 2(-/-) mice before the development of signs of colitis. CD14 mRNA and protein expression in the epithelial cells of colitic mice were confirmed by RT-PCR and Western blot analysis of isolated cells. In addition, IL-2(-/-) mice also expressed increased levels of IL-15 mRNA in small intestinal and colonic epithelial cells compared with heterozygous control mice. TNF-α, IL-1β, IL- 6, KC, and JE mRNAs were only detectable in colonic epithelial cells of mice after the onset of colitis. Enhanced expression of TGF-β1, IL-15, and CD14 by colonic epithelial cells may play a role in the subsequent development of colitis in IL-2(-/-) mice.
AB - Intestinal epithelial cells may be actively involved in the immunoregulatory pathways leading to intestinal inflammation. The aim of this study was to assess expression by intestinal epithelial cells of cytokines with potential involvement in the development of intestinal inflammation in interleukin (IL)-2-deficient [(-/-)] mice. Wild-type mice, mice heterozygous for the disrupted IL-2 gene, and IL-2(-/-) mice were studied at 6, 16, and 24 wk of age. The mRNA levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), IL-1β, IL-6, IL-15, KC, JE, and CD14 in colonic and small intestinal epithelial cells were assessed by Northern blot analysis. CD14 was also measured by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). TGF-β1 mRNA was constitutively expressed in both colonic and small intestinal epithelial cells with increased expression in the colonic epithelium of colitic mice. CD14 was detected only in colonic epithelial cells, and mRNA levels increased severalfold in IL-2(-/-) mice with colitis. Northern analysis demonstrated increased levels of TGF-β1 and CD14 mRNA in colonic epithelial cells of IL- 2(-/-) mice before the development of signs of colitis. CD14 mRNA and protein expression in the epithelial cells of colitic mice were confirmed by RT-PCR and Western blot analysis of isolated cells. In addition, IL-2(-/-) mice also expressed increased levels of IL-15 mRNA in small intestinal and colonic epithelial cells compared with heterozygous control mice. TNF-α, IL-1β, IL- 6, KC, and JE mRNAs were only detectable in colonic epithelial cells of mice after the onset of colitis. Enhanced expression of TGF-β1, IL-15, and CD14 by colonic epithelial cells may play a role in the subsequent development of colitis in IL-2(-/-) mice.
KW - CD14
KW - Interleukin-15
KW - Lipopolysaccharide
KW - Transforming growth factor-β
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U2 - 10.1152/ajpgi.1998.274.3.g472
DO - 10.1152/ajpgi.1998.274.3.g472
M3 - Article
C2 - 9530147
AN - SCOPUS:0031954425
SN - 0193-1857
VL - 274
SP - G472-G479
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 3 37-3
ER -