Abstract
The immunologic signals participating in immune responses early in life have not been completely elucidated. Regarding the characterization of neonatal cells, little is known concerning the activity of transcription factor nuclear factor kappa B (NF-κB), which regulates inflammatory genes and cytokine production. The aim of this study was to characterize NF-κB activation in cord blood mononuclear cells (CBMC). We analyzed the potential association of NF-κB activity with lymphocyte proliferation and influences on cytokine secretion in the early immune system. To determine the contribution of a disease whereby inheritance may impact neonatal immunity, we assessed the influence of maternal allergic disease on NF-κB regulation and cytokine secretion. CBMC from healthy newborns were isolated and stimulated with mitogen (n = 28). Nuclear extracts were analyzed by electrophoretic mobility shift assay, cytokine secretion by ELISA. FISH analysis excluded relevant maternal contamination of CBMC. All samples showed a positive lymphoproliferative response, and NF-κB activity was both increased and decreased after mitogen stimulation. Increased NF-κB activation was significantly associated with decreased TNF-α secretion (median 6.1 versus 50.3 pg/mL) in unstimulated CBMC. Mitogen stimulation resulted in increased NF-κB activity with a trend to increased IL-13 production. Maternal allergic disease was associated with higher TNF-α (median 982 versus 173 pg/mL) and IL-13 secretion (median 1328 versus 1120 pg/mL) after mitogen stimulation. Together, NF-κB activity is differentially activated in cord blood and associated with a distinct cytokine pattern. Whether differential NF-κB activity in cord blood is related to the subsequent development of immune diseases requires further investigation.
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Abbreviations
- CBMC:
-
cord blood mononuclear cells
- EMSA:
-
electrophoretic mobility shift assay
- IFN-γ:
-
interferon gamma
- NF-κB:
-
nuclear factor kappa B
- PHA:
-
phytohemagglutinin
- SI:
-
stimulation index
- Th:
-
T helper
- TNF-α:
-
tumor necrosis factor alpha
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Acknowledgements
The authors thank the participants and staff of Project Viva, Diane Sredl for program assistance, and Craig Lilly, Fiona Gibbons, and Abdel Bellou for critical review of the manuscript.
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Supported by grant 5R01AI045007–04, HD 34568, HL 64925, HL 68041, HL 61907, DFG 711/1–1.
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Schroeter, C., Schaub, B., Gold, D. et al. Nuclear Factor Kappa B Activation in Human Cord Blood Mononuclear Cells. Pediatr Res 56, 212–218 (2004). https://doi.org/10.1203/01.PDR.0000132850.33375.D0
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DOI: https://doi.org/10.1203/01.PDR.0000132850.33375.D0
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