Interferon-gamma tempers the expression of carcinoembryonic antigen family molecules in human colon cells: a possible role in innate mucosal defence.
Four carcinoembryonic antigen-related cell adhesion molecule (CEACAM)s, i.e. CEA, CEACAM1, CEACAM6 and CEACAM7, are localized to the apical glycocalyx of normal colonic epithelium and have been suggested to play a role in innate immunity. The expression of these molecules in colon carcinoma cells was studied at the mRNA and protein levels after treatment with interferon-gamma (IFN-gamma), interleukin-1beta, live bacteria or lipopolysaccharide. The colon carcinoma cell lines LS174T and HT-29 were studied in detail using real-time quantitative reverse transcriptase-polymerase chain reaction, immunoflow cytometry and immunoelectron microscopy. IFN-gamma, but not the other agents, modified expression of CEA, CEACAM1 and CEACAM6. None of the agents upregulated CEACAM7 expression. Two expression patterns were seen. HT-29 cells, which initially showed low quantities of mRNAs and proteins, displayed marked upregulation of both mRNAs and proteins. LS174T cells transcribed stable high levels of mRNA before and after treatment. Additionally, IFN-gamma induced increased cell surface expression of CEA, CEACAM1 and CECAM6. IFN-gamma has two important effects on the expression levels of the CEA family molecules in colon epithelial cells: direct upregulation of CEACAM1 and promotion of cell differentiation resulting in increased expression of CEA and CEACAM6 and decreased expression of CEACAM7.
Fahlgren
A
A
Department of Immunology, Umeå University, Umeå, Sweden.
Baranov
V
V
Frängsmyr
L
L
Zoubir
F
F
Hammarström
M-L
ML
Hammarström
S
S
D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003106:Colon / Q000276:immunology*; D058851:GPI-Linked Proteins; D019073:HT29 Cells; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; C069847:CD66 antigens; C504117:CEACAM6 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D007371:Interferon-gamma