Direct effects of IL-4/IL-13 and the nematode Nippostrongylus brasiliensis on intestinal epithelial cells in vitro.
Nematode infections induce the upregulation of mucin- and glycosylation-related genes in intestinal epithelial cells in vivo. However, the factor(s) that induce these changes in epithelial cells have not been fully elucidated. In the present study, we analysed the effects of the Th2 cytokines IL-4 and IL-13 and the excretory-secretory (ES) product of the nematode Nippostrongylus brasiliensis on the gene expression of the major mucin core peptide MUC2, the sialyltransferase ST3GalIV (Siat4c) and the sulphotransferase HS3ST1 in intestinal epithelium-derived IEC-6 cells by quantitative reverse transcription (RT)-PCR. The administration of IL-4 and IL-13 resulted in a significant upregulation of ST3GalIV and HS3ST1 gene transcription, but had no effect on MUC2, in IEC-6 cells. RT-PCR studies also demonstrated the constitutive expression of IL-13Ralpha1 and IL-4R in IEC-6 cells. On the other hand, the ES product induced upregulation of ST3GalIV, but not HS3ST1 or MUC2, while coadministration of IL-13 and the ES product induced a slight but significant upregulation of MUC2. Co-incubation of live N. brasiliensis adult worms with IEC-6 cells resulted in the upregulation of ST3GalIV and MUC2. These results suggested that HS3ST1 gene expression is strictly regulated by IL-4/IL-13, while ST3GalIV and MUC2 gene expressions are regulated by redundant mechanisms.
Takeda
K
K
Department of Medical Zoology, Kyoto Prefectural University of Medicine, Kyoto, Japan. k-takeda@koto.kpu-m.ac.jp
Hashimoto
K
K
Uchikawa
R
R
Tegoshi
T
T
Yamada
M
M
Arizono
N
N
D000818:Animals; D000947:Antigens, Helminth / Q000502:physiology; D004847:Epithelial Cells / Q000276:immunology / Q000469:parasitology; D020869:Gene Expression Profiling; D007082:Ileum / Q000276:immunology / Q000469:parasitology*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D055262:Mucin-2 / Q000096:biosynthesis*; D009559:Nippostrongylus / Q000472:pathogenicity*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012799:Sialyltransferases / Q000096:biosynthesis*; D015238:Sulfotransferases / Q000096:biosynthesis*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D000947:Antigens, Helminth; D018793:Interleukin-13; C524628:Muc2 protein, rat; D055262:Mucin-2; D015847:Interleukin-4; D012799:Sialyltransferases; D015238:Sulfotransferases; C021350:heparitin sulfotransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase