IFN-gamma impairs release of IL-8 by IL-1beta-stimulated A549 lung carcinoma cells
- 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-kappaBalpha, 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.
Verfasserangaben: | Kim Alexander Boost, Christian David Sadik, Malte BachmannGND, Bernhard ZwißlerGND, Josef PfeilschifterGND, Heiko MühlORCiDGND |
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URN: | urn:nbn:de:hebis:30-57481 |
DOI: | https://doi.org/10.1186/1471-2407-8-265 |
ISSN: | 1471-2407 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/18801189 |
Titel des übergeordneten Werkes (Englisch): | BMC Cancer |
Verlag: | BioMed Central |
Verlagsort: | London |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 18.09.2008 |
Datum der Erstveröffentlichung: | 18.09.2008 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 19.08.2009 |
Jahrgang: | 8 |
Ausgabe / Heft: | 265 |
Seitenzahl: | 8 |
Erste Seite: | 1 |
Letzte Seite: | 8 |
Bemerkung: | © 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
HeBIS-PPN: | 21490895X |
Institute: | Medizin / Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Lizenz (Deutsch): | Creative Commons - Namensnennung 2.0 |