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Updated: Jun 15, 2026
Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
Cardiotrophin-1 induces tumor necrosis factor alpha synthesis in human peripheral blood mononuclear cells
Michael Fritzenwanger1, Katharina Meusel, Christian Jung
1Division of Cardiology, Department of Internal Medicine I, Friedrich-Schiller-University of Jena, Erlanger Allee 101, 07740 Jena, Germany. michael.fritzenwanger@med.uni-jena.de
Insights
Cardiotrophin-1 (CT-1) stimulates tumor necrosis factor-alpha (TNFα) production in peripheral blood mononuclear cells (PBMC). This finding reveals a new mechanism for elevated TNFα in chronic heart failure (CHF) beyond gut bacterial translocation.
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Chronic heart failure (CHF) is linked to increased tumor necrosis factor-alpha (TNFα) and cardiotrophin-1 (CT-1) levels.
- Peripheral blood mononuclear cell (PBMC) function is altered in CHF patients.
Purpose of the Study:
- To investigate if CT-1 can induce TNFα production in PBMCs from healthy individuals.
- To elucidate the molecular mechanisms underlying CT-1-induced TNFα expression.
Main Methods:
- PBMCs were treated with varying concentrations and durations of CT-1.
- TNFα protein and mRNA levels were quantified using ELISA and real-time PCR.
- Immunofluorescent flow cytometry, actinomycin D, brefeldin A, and parthenolide were used to study the mechanisms involved.
- Nuclear factor-kappaB (NFκB) translocation was assessed.
Main Results:
- CT-1 dose- and time-dependently induced TNFα protein and mRNA in PBMCs.
- Maximal TNFα protein and mRNA induction occurred at 100 ng/mL CT-1 after 3-6 hours and 1 hour, respectively.
- Protein synthesis, intracellular transport, and NFκB translocation were essential for CT-1-induced TNFα expression.
Conclusions:
- CT-1 is a potent inducer of TNFα in human PBMCs.
- This study presents a novel mechanism for elevated serum TNFα in CHF, independent of bacterial translocation.
- NFκB activation plays a critical role in CT-1-mediated TNFα production.
Abstract:
Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) alpha and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNFalpha in PBMC of healthy volunteers. CT-1 induced in PBMC TNFalpha protein in the supernatant and TNFalpha mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNFalpha protein was achieved with 100 ng/mL CT-1 after 3-6 hours and maximal TNFalpha 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 TNFalpha expression. CT-1 caused a dose dependent nuclear factor (NF) kappaB translocation. Parthenolide inhibited both NFkappaB translocation and TNFalpha protein expression indicating that NFkappaB seems to be necessary. We revealed a new mechanism for elevated serum TNFalpha concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut.
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