Cardiac glycoside inhibits IL-8-induced biological responses by downregulating IL-8 receptors through altering membrane fluidity.

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Manna SK, Sreenivasan Y, Sarkar A

Cardiac glycoside inhibits IL-8-induced biological responses by downregulating IL-8 receptors through altering membrane fluidity.

J Cell Physiol. 2006 Apr;207(1):195-207. doi: 10.1002/jcp.20555.

PubMed ID

16331685 [ View in PubMed

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Abstract

Considering the potential role of interleukin-8 (IL-8) in inflammation, angiogenesis, tumorogenesis, and metastasis, and the involvement of different cell types especially neutrophils and macrophages in those processes, the regulation of IL-8-mediated biological responses is important. In this report we provide evidences that oleandrin, a cardiac glycoside potentially inhibited IL-8-, formyl peptide (FMLP)-, EGF-, or nerve growth factor (NGF)-, but not IL-1- or TNF-induced NF-kappaB activation in macrophages. Oleandrin inhibited IL-8-, but not TNF-induced NF-kappaB-dependent genes expression. Oleandrin inhibited the binding of IL-8, EGF, or NGF, but not IL-1 or TNF. It decreased almost 79% IL-8 binding without altering affinity towards IL-8 receptors and this inhibition of IL-8 binding was observed in isolated membrane. The IL-8, anti-IL-8Rs antibodies, or protease inhibitors were unable to protect oleandrin-mediated inhibition of IL-8 binding. Phospholipids significantly protected oleandrin-mediated inhibition of IL-8 binding thereby restoring IL-8-induced NF-kappaB activation. Oleandrin altered the membrane fluidity as detected by microviscosity parameter and a decrease in diphenylhexatriene, a lipid binding fluorophore binding in a dose-dependent manner. Overall, our results suggest that oleandrin inhibits IL-8-mediated biological responses in diverse cell types by modulating IL-8Rs through altering membrane fluidity and microviscosity. The study might help to regulate IL-8-mediated biological responses involved in inflammation, metastasis, and neovascularization.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Oleandrin	Beta-nerve growth factor	Protein	Humans	Unknown	Inhibitor	Details
Oleandrin	Interleukin-8	Protein	Humans	Unknown	Inhibitor	Details
Oleandrin	Pro-epidermal growth factor	Protein	Humans	Unknown	Inhibitor	Details