Cardiotrophin-1 Induces Tumor Necrosis Factor α Synthesis in Human Peripheral Blood Mononuclear Cells. (10th March 2010)

• Record Type: Journal Article
• Authors: Fritzenwanger, Michael; Meusel, Katharina; Jung, Christian; Franz, Marcus; Wang, Zhenhua; Foerster, Martin; Figulla, Hans-R.
• Other Names: Campbell Charles Larry Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2009(2009)
• Publication Date: 2010-03-10
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2009/489802
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : 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) κ B translocation. Parthenolide inhibited both NFκ B translocation and TNFα protein expression indicating that NFκ B 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.