title: IFN-gamma impairs release of IL-8 by IL-1beta-stimulated A549 lung carcinoma cells.
abstract: BACKGROUND
  Production of interferon (IFN)-gamma is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNgamma on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells.
  
  
  METHODS
  A549 cells were cultured and stimulated with interleukin (IL)-1beta alone or in combination with IFNgamma. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA). mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA), respectively. Expression of inhibitor-kappa Balpha, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis.
  
  
  RESULTS
  Here we demonstrate that IFNgamma efficiently reduced IL-8 secretion under the influence of IL-1beta. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNgamma on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNgamma on IL-1beta-induced NF-kappaB activation as assessed by cellular IkappaB levels. Moreover, analysis of intracellular IL-8 suggests that IFNgamma modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1beta-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNgamma indicating that modulation of IL-1beta action by this cytokine displays specificity.
  
  
  CONCLUSIONS
  Data presented herein agree with an angiostatic role of IFNgamma as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1)-like functions in lung cancer patients e.g. by local delivery of IFNgamma may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8.
authors.affiliation: Klinik für Anaesthesiologie, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377 Munich, Germany. kim.boost@med.uni-muenchen.de
authors.forename: Kim A
authors.initials: KA
authors.lastname: Boost
authors.forename: Christian D
authors.initials: CD
authors.lastname: Sadik
authors.forename: Malte
authors.initials: M
authors.lastname: Bachmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zwissler
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: Heiko
authors.initials: H
authors.lastname: Mühl
mesh_terms: D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D007371:Interferon-gamma; D051546:Cyclooxygenase 2
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