Interleukin-4 induces specific pp-GalNAc-T expression and alterations in mucin O-glycosylation in colonic epithelial cells.
Mucus hypersecretion occurs as a consequence of the Th2 immune response in epithelia, yet it was not previously known whether the degree of O-glycosylation was modulated under such conditions. A colonic carcinoma cell line LS174T was used to assess the effect of interleukin (IL)-4 on the mRNA levels of eight pp-GalNAc-Ts. A three- to four-fold increase in pp-GalNAc-T1, T4, and T7 levels was observed. Lysates of untreated or IL-4-treated cells were examined for their ability to transfer GalNAc residues onto a peptide corresponding to the tandem repeat portion of human MUC2. The number of incorporated GalNAc residues was greater after incubation with lysates of IL-4-treated cells than with lysates of untreated cells. Mucin-like large glycoproteins secreted by IL-4-treated cells had higher binding capacity to PNA and VVA-B(4) than those secreted by untreated cells. The results indicated that IL-4-treated LS174T cells are able to produce mucins with a higher degree of O-glycosylation than untreated counterparts.
Kanoh
Akira
A
Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takeuchi
Hideyuki
H
Kato
Kentaro
K
Waki
Michihiko
M
Usami
Katsuaki
K
Irimura
Tatsuro
T
D015153:Blotting, Western; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008970:Molecular Weight; D009077:Mucins / Q000378:metabolism*; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D015847:Interleukin-4; D007527:Isoenzymes; D037102:Lectins; D009077:Mucins; D017350:N-Acetylgalactosaminyltransferases; D012333:RNA, Messenger; D000097763:Polypeptide N-acetylgalactosaminyltransferase