Cardiotrophin-1 Induces Tumor Necrosis Factor α Synthesis in Human Peripheral Blood Mononuclear Cells

Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) α and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNFα in PBMC of healthy volunteers. CT-1 induced in PBMC TNFα pr...

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Bibliographic Details
Published in:Mediators of Inflammation 2009-01, Vol.2009 (2009), p.319-325
Main Authors: Fritzenwanger, Michael, Meusel, Katharina, Jung, Christian, Franz, Marcus, Wang, Zhenhua, Foerster, Martin, Figulla, Hans Reiner
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cells, Cultured
Cytokines - metabolism
Development and progression
General aspects
Health aspects
Heart failure
Heart Failure - metabolism
Humans
Leukocytes, Mononuclear - cytology
Leukocytes, Mononuclear - metabolism
Medical sciences
NF-kappa B - metabolism
Protein biosynthesis
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tumor necrosis factor
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
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Summary:Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) α and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNFα in PBMC of healthy volunteers. CT-1 induced in PBMC TNFα protein in the supernatant and TNFα mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNFα protein was achieved with 100 ng/mL CT-1 after 3–6 hours and maximal TNFα mRNA induction after 1 hour. ELISA data were confirmed using immunofluorescent flow cytometry. Inhibitor studies with actinomycin D and brefeldin A showed that both protein synthesis and intracellular transport are essential for CT-1 induced TNFα expression. CT-1 caused a dose dependent nuclear factor (NF) κB translocation. Parthenolide inhibited both NFκB translocation and TNFα protein expression indicating that NFκB seems to be necessary. We revealed a new mechanism for elevated serum TNFα concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut.
ISSN:0962-9351
1466-1861
DOI:10.1155/2009/489802