Modulatory Effect of Cytokines on Glycolipid Expression of Human Glioma Cell Line U118MG : Changeable response and gradual loss of sensitivity to cytokines of glioma cells in culture
The effect of immune cytokines on the composition of neutral and acidic glycolipids was analyzed. Untreated U118MG cells expressed four kinds of neu-tral glycolipid molecules (CMH, CDH, CTH, and Gb?Cer), and two kinds of acidic glycolipid (GM3 and GM2) as its major components. Effect of immune cytokines on the composition of the glycolipid composition was analyzed. U118MG cells were grown subconfiuently before a panel of cytokines (IL-lbeta, 100U/ml ; IL-2, 4000JRU/ml ; IL-4, 100U/ml ; IL-6, 100 ng/ml ; IL-8, 100 ng/ ml ; IFN-alpha, 1000U/ml ; IFN-beta, 1000U/ml ; IFN-gamma, 1000U/ml ; TNF- alpha 10U/ml, and G-CSF 2 ng/ml) were pulsed for 48 hrs. In the neutral glycolipids new bands supposed to be subspecies of CMH and CDH with different fatty acid chains were recognized in the cells treated with IFN-alpha, IL-4, IL-6 and IL-8, although no constitutional change of sugar moieties was noted. In the acidic ones, IFN-gamma and IL-4 treatment brought about remarkable changes in the glycolipid profile enhancing sulfatides, GM1, GD1a, GD1b, and GT1b of the acidc lipids, with or without GM2 and GM3 expression. TNF-alpha also induced GM1. Repeated experiments with the same culture conditions revealed different responses to cytokines in the expression of subspecies of CMH and CDH, and significant changes in the acidic glycolipids were noted in IL-2, G-CSF, TNF-alpha and IL-4 treatment. The 3rd series of repeated experiments using TNF-alpha, IFN-gamma, IL-4 and IL-6 showed only induction of subspecies of CMH by IFN-gamma ; no alteration of acidic glycolipid profile was noted. The 4th series of the same experiments in the same conditions resulted in no response. Raising the dose of cytokines, change of the passage of the cells, addition of DMSO (a potent differentiation factor) did not restore the sensitivity to the cyto-kines. Similar experiments using 6 other glioma cell lines and one melanoma cell line did not induce any glycolipid modulation. We believe that glioma cells have the potential to respond to certain cytokines to modulate their glycolipid expression under undetermined special conditions, and they are biologically unsta-ble in terms of cytokine sensitivity in culture
