Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors.
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Raviprakash N, Manna SK
Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors.
Br J Pharmacol. 2014 Jul;171(14):3339-51. doi: 10.1111/bph.12493.
- PubMed ID
- 24172227 [ View in PubMed]
- Abstract
BACKGROUND AND PURPOSE: One of the first steps in host defence is the migration of leukocytes. IL-8 and its receptors are a chemokine system essential to such migration. Up-regulation of these receptors would be a viable strategy to treat dysfunctional host defence. Here, we studied the effects of the plant glycoside oleandrin on responses to IL-8 in a human monocytic cell line. EXPERIMENTAL APPROACH: U937 cells were incubated with oleandrin (1-200 ng mL(-1) ) for either 1 h (pulse) or for 24 h (non-pulse). Apoptosis; activation of NF-kappaB, AP-1 and NFAT; calcineurin activity and IL-8 receptors (CXCR1 and CXCR2) were measured using Western blotting, RT-PCR and reporter gene assays. KEY RESULTS: Pulse exposure to oleandrin did not induce apoptosis or cytoxicity as observed after non-pulse exposure. Pulse exposure enhanced activation of NF-kappaB induced by IL-8 but not that induced by TNF-alpha, IL-1, EGF or LPS. Exposure to other apoptosis-inducing compounds (azadirachtin, resveratrol, thiadiazolidine, or benzofuran) did not enhance activation of NF-kappaB. Pulse exposure to oleandrin increased expression of IL-8 receptors and chemotaxis, release of enzymes and activation of NF-kappaB, NFAT and AP-1 along with increased IL-8-mediated calcineurin activation, and wound healing. Pulse exposure increased numbers of cell surface IL-8 receptors. CONCLUSIONS AND IMPLICATIONS: Short-term (1 h; pulse) exposure to a toxic glycoside oleandrin, enhanced biological responses to IL-8 in monocytic cells, without cytoxicity. Pulse exposure to oleandrin could provide a viable therapy for those conditions where leukocyte migration is defective.