The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases the level of galectin-3-specific mRNA in HCT-8 cells.
OBJECTIVE
Galectin-3, a lectin with specificity for beta galactoside, is expressed by a variety of cells, including intestinal epithelial cells. Among other functions, galectin-3 mediates cell adhesion and is involved in inflammatory processes. In this study, we assessed the expression of galectin-3 in intestinal epithelial cells from Crohn's disease patients (n = 10), ileum adjacent to resected colon carcinoma (n = 9), unspecific bowel inflammation (n = 1), diverticulosis (n = 1), ulcerative colitis (n = 3) and healthy jejunum used for interposition in larynx carcinoma (n = 1). The role of cytokines on galectin-3 expression was a further aim of our study.


METHODS
The galectin-3 distribution in intestinal epithelia was analysed by immunohistochemistry, immunoblotting, immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR). Human intestinal epithelial cell line (HCT-8) and primary cultured intestinal epithelial cells were treated with cytokines, and the effects on galectin-3 expression were determined by RT-PCR.


RESULTS
Galectin-3 showed a homogeneous distribution in epithelia from control patients. In contrast, in epithelial cells from Crohn's disease lesions, galectin-3 staining was strongly spotted and heterogeneous. In inflamed and reorganized tissue, galectin-3 expression was markedly reduced, and was associated with disintegration of epithelia. Primary cultured epithelial cells as well as HCT-8 cells expressed galectin-3 protein and mRNA. Incubation of HCT-8 cells with tumour necrosis factor alpha (TNF-alpha), but not with other cytokines, substantially reduced galectin-3 expression as shown by semiquantitative RT-PCR.


CONCLUSIONS
Downregulation of galectin-3 in the intestinal epithelium of Crohn's disease patients may be a consequence of enhanced TNF-alpha production by inflammatory cells, thereby contributing to the pathophysiology of the disease.
Jensen-Jarolim
Erika
E
Department of Pathophysiology, University of Vienna, Vienna, Austria.
Gscheidlinger
Regina
R
Oberhuber
Georg
G
Neuchrist
Czilla
C
Lucas
Trevor
T
Bises
Giovanna
G
Radauer
Christian
C
Willheim
Martin
M
Scheiner
Otto
O
Liu
Fu-Tong
FT
Boltz-Nitulescu
George
G
D000943:Antigens, Differentiation / Q000378:metabolism*; D002460:Cell Line; D003424:Crohn Disease / Q000378:metabolism*; D016207:Cytokines; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D037502:Galectin 3; D006801:Humans; D007082:Ileum / Q000166:cytology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000943:Antigens, Differentiation; D016207:Cytokines; D037502:Galectin 3; D012333:RNA, Messenger