Tumour necrosis factor-alpha decreases expression of the intestinal IgG Fc binding site by HT29-N2 cells.
Previously, we describe a unique binding site for the Fc region of IgG in human intestinal goblet cells, but regulation of the intestinal IgG Fc binding site (Fc gamma IBS) has not been clarified. In this work, we examined the effects of tumour necrosis-alpha (TNF-alpha) and interferon gamma (IFN-gamma) on expression of the Fc gamma IBS in HT29-N2 colonic cancer cells, which differentiate readily into goblet cells containing the binding site when grown in galactose-containing medium. Expression of the site was monitored immunocytochemically and by ELISA on homogenates of the cells. TNF-alpha in doses of 0.1-100 ng/ml caused a reduction in expression of the Fc gamma IBS and the proportion of cells positive for mucin (as demonstrated by Alcian blue stain), without affecting the viability of the cells. The effects of TNF-alpha on the FC gamma IBS and mucin production could not be attributed to a decreased proliferative rate of the cells, as the cells' incorporation of 5-bromo-2'-deoxyuridine was unaffected. By contrast with TNF-alpha, IFN-gamma (i) did not affect the proportion of cells expressing the Fc gamma IBS, (ii) decreased the viability of the cells, and (iii) increased cell proliferation. Additional evidence of specificity of the TNF-alpha effect on the Fc gamma IBS was that TNF-alpha did not affect expression of the polymeric immunoglobulin receptor (secretory component), whereas IFN-gamma increased it. We conclude that TNF-alpha may suppress expression of the Fc gamma IBS by colonocytes and oppose differentiation of the cells towards mucin-producing cells.
Hamada
Y
Y
Department of Medicine, Veterans Affairs Medical Center, Denver, CO 80220.
Kobayashi
K
K
Brown
W R
WR
D001666:Binding Sites, Antibody / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003106:Colon / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007124:Immunoenzyme Techniques; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma