IFN-gamma impairs release of IL-8 by IL-1 beta-stimulated A549 lung carcinoma cells

IFN-gamma impairs release of IL-8 by IL-1 beta-stimulated A549 lung carcinoma cells

Beschreibung

vor 16 Jahren
Background: Production of interferon (IFN)-gamma is key to
efficient anti-tumor immunity. The present study was set out to
investigate effects of IFN. 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)-1 beta alone or in combination with IFN gamma. 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
B alpha, cellular IL-8, and cyclooxygenase-2 was analyzed by
Western blot analysis. Results: Here we demonstrate that IFN gamma
efficiently reduced IL-8 secretion under the influence of IL-1
beta. Surprisingly, real-time PCR analysis and RPA revealed that
the inhibitory effect of IFN gamma on IL-8 was not associated with
significant changes in mRNA levels. These observations concurred
with lack of a modulatory activity of IFN gamma on IL-1
beta-induced NF-kappa B activation as assessed by cellular I kappa
B levels. Moreover, analysis of intracellular IL-8 suggests that
IFN gamma modulated IL-8 secretion by action on the
posttranslational level. In contrast to IL-8, IL-1 beta-induced
cyclooxygenase-2 expression and release of IL-6 were not affected
by IFN gamma indicating that modulation of IL-1 beta action by this
cytokine displays specificity. Conclusion: Data presented herein
agree with an angiostatic role of IFN gamma as seen in rodent
models of solid tumors and suggest that increasing T helper type I
(Th1)-like functions in lung cancer patients e.g. by local delivery
of IFN gamma may mediate therapeutic benefit via mechanisms that
potentially include modulation of pro-angiogenic IL-8.

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