title: Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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-κB, AP-1 and NFAT; calcineurin activity and IL-8 receptors (CXCR1 and CXCR2) were measured using Western blotting, RT-PCR and reporter gene assays.
  
  
  RESULTS
  Pulse exposure to oleandrin did not induce apoptosis or cytoxicity as observed after non-pulse exposure. Pulse exposure enhanced activation of NF-κB induced by IL-8 but not that induced by TNF-α, IL-1, EGF or LPS. Exposure to other apoptosis-inducing compounds (azadirachtin, resveratrol, thiadiazolidine, or benzofuran) did not enhance activation of NF-κB. Pulse exposure to oleandrin increased expression of IL-8 receptors and chemotaxis, release of enzymes and activation of NF-κB, 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
  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.
authors.affiliation: Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics (CDFD), Hyderabad, 500 001, India.
authors.forename: Nune
authors.initials: N
authors.lastname: Raviprakash
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Manna
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002298:Cardenolides / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D019169:Jurkat Cells; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D061986:MCF-7 Cells; D053700:Receptors, Interleukin-8 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D002298:Cardenolides; D016209:Interleukin-8; D053700:Receptors, Interleukin-8; C021065:oleandrin
keywords: IL-8 receptor; NF-κB; apoptosis; cardiac glycoside; chemotaxis