The influence of tumour necrosis factor-alpha, interleukin-1 beta and interferon-gamma on the expression and function of the complement regulatory protein CD59 on the human colonic adenocarcinoma cell line HT29.
CD59 is a 18-25 kDa glycoprotein which, by inhibiting the formation of the membrane attack complex, protects homologous cells from complement mediated damage. We have described recently the expression and complement regulatory function of CD59 on colonic adenocarcinoma cells both in vivo and in vitro. In this study we have examined the influence of cytokines on the expression and complement regulatory function of CD59 on the colonic adenocarcinoma cell line HT29. CD59 expression on the HT29 cells was up-regulated after stimulation by mononuclear cells activated by mixed lymphocyte reaction and by culture supernatants from activated mononuclear cells. Similarly, a dose-dependent increase in CD59 expression was observed after stimulation with both tumour necrosis factor-alpha and interleukin-1 beta. A dose-dependent increase in the level of CD59 expression was also seen using low concentrations of interferon-gamma (IFN-gamma), while CD59 expression on cells cultured with high IFN-gamma concentrations was comparable to non-stimulated cells. Cytokine treated cells were more resistant to lysis by homologous complement than non-stimulated cells, and the increase in CD59 expression was shown to be partially responsible for this. The present data strengthen the role of CD59 as a possible participant in tumour escape.
Bjørge
L
L
Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway.
Jensen
T S
TS
Ulvestad
E
E
Vedeler
C A
CA
Matre
R
R
D000230:Adenocarcinoma / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D018957:CD59 Antigens; D003110:Colonic Neoplasms / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000096:biosynthesis* / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003165:Complement System Proteins