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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 474533.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Amplification of lipopolysaccharide-induced cytokine synthesis in non-small cell lung cancer/neutrophil cocultures
Authors:Grandel, U.; Heygster, D.; Sibelius, U.; Fink, L.; Sigel, S.; Seeger, W.; Grimminger, F.; Hattar, K.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Mol Cancer Res
Volume:7
Issue / Number:10
Start Page:1729
End Page:35
Audience:Not Specified
Abstract / Description:Proinflammatory cytokines are centrally involved in tumor progression and survival in non-small cell lung cancer, and both the presence of infiltrating neutrophils and bacterial infection in the lung may indicate a poor prognosis. Against this background, we investigated the effect of the bacterial cell wall component lipopolysaccharide (LPS) on interleukin (IL)-6 and IL-8 synthesis in the non-small cell lung cancer line A549 and in A549-neutrophil cocultures. The LPS induced a dose-dependent and time-dependent release of IL-8 from A549 cells, whereas IL-6 could not be detected. Interestingly, in A549-neutrophil cocultures, IL-8 synthesis was massively amplified and IL-6 was also released, compared with the respective monocultures. The A549 cells were identified as the primary cellular source of these cytokines, as enhanced cytokine mRNA transcription was detected in this cell type, although not in neutrophils in the coculture system. Experiments done in transwells indicated that direct cell-cell contact was a prerequisite for the increased cytokine generation. Inhibition of tumor necrosis factor-alpha bioactivity by neutralizing antibodies and blocking cyclooxygenase-2 activity blunted the enhanced cytokine generation in the coculture system. Amplification of LPS-induced cytokine secretion could be reproduced when the small cell lung cancer cell line H69 was cocultured with neutrophils. When the Gram-positive cell wall component lipoteichoic acid was used instead of LPS, cytokine synthesis was also amplified in A549-neutrophil cocultures, to a similar extent to that observed with LPS. These data indicate that interaction between bacterial pathogens, neutrophils, and tumor cells might amplify the release of proinflammatory cytokines which may promote tumor growth in vivo.
Free Keywords:Carcinoma, Non-Small-Cell Lung/genetics/*immunology/physiopathology; Cell Communication/immunology; Cell Line, Tumor; Cells, Cultured; Chemotaxis, Leukocyte/drug effects/immunology; Coculture Techniques; Cyclooxygenase 2 Inhibitors/pharmacology; Cytokines/*biosynthesis; Disease Progression; Dose-Response Relationship, Drug; Humans; Inflammation/genetics/*immunology/physiopathology; Inflammation Mediators/pharmacology; Interleukin-6/biosynthesis; Interleukin-8/biosynthesis/drug effects; Lipopolysaccharides/*pharmacology; Lung Neoplasms/genetics/*immunology/physiopathology; Neutrophils/drug effects/*immunology; Pneumonia, Bacterial/complications/immunology/physiopathology; RNA, Messenger/metabolism; Teichoic Acids/pharmacology; Time Factors; Transcriptional Activation/drug effects
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Internal Medicine V, University of Giessen Lung Center, Giessen, Germany.
Identifiers:ISSN:1557-3125 (Electronic) 1541-7786 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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