METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in high and low glucose concentrations. All HUVECs were treated with different concentrations of isoproterenol and propranolol for different time periods. The analytical procedures consisted of Western Blot, ELISA, DCFH-DA and TUNEL assays.
RESULTS: Isoproterenol (agonist of a beta-adrenergic receptor) significantly reduced phosphorylation at Ser-536 of NF-κB; and Ser-32 and Ser-36 of IκBα in hyperglycemic HUVECs. Isoproterenol also significantly reduced apoptosis and ROS generation. No effect of IκBα was observed on Tyr-42 phosphorylation. The effect of isoproterenol was reversed by the antagonist propranolol. We also checked if NF-κB inhibitor MG132 causes any change at the level of apoptosis. However, we observed an almost similar effect.
CONCLUSION: Given data demonstrates that beta-adrenergic receptors stimulation has a protective effect on HUVECs that might be occuring via NF-κβ and IκBα pathway.
RESULTS: Anti-ICAM-1 and CD36 monoclonal antibodies were able to inhibit and reverse P. falciparum binding of lab and recently adapted patient isolates in vitro. However, reversal of binding was incomplete and varied in its efficiency between parasite isolates.
CONCLUSIONS: The results show that, as a proof of concept, disturbing existing ligand-receptor interactions is possible and could have potential therapeutic value for severe malaria. The variation seen in the degree of reversing existing binding with different parasite isolates and the incomplete nature of reversal, despite the use of high affinity inhibitors, suggest that anti-adhesion approaches as adjunct therapies for severe malaria may not be effective, and the focus may need to be on inhibitory approaches such as vaccines.