TNFα regulates the localization of CD40 in lipid rafts of glioma cells

Resistance of glioblastoma multiforme (GBM) to TNF alpha induced apoptosis is attributed to NF kappa B activation. As TNF-receptor family member CD40 regulates NF kappa B activation, we investigated the role of CD40 in NF kappa B activation in GBM. We observed elevated CD40 levels in human glioma samples as compared to the surrounding normal tissue. Treatment with TNF alpha elevated CD40 levels in glioma cells and inhibition of CD40 signaling failed to abrogate TNF alpha induced NF kappa I' activity. While TNF alpha increased the interaction between TRAF2/6, I kappa B alpha, IKK alpha/beta in the CD40 signalosome, the level of CD40 in the signalosome remained unaffected upon TNF alpha treatment. Interestingly, TNF alpha decreased the spatial localization of CD40 and increased TRAF2/6 co-localization with lipid raft marker Caveolin. As localization of CD40 signalosome in lipid raft is crucial for NF kappa B activation, TNF alpha mediated decreased clustering of CD40 in lipid rafts could have possibly contributed to its non-involvement in NF kappa B activation.