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IL-1 beta and TGF beta 2 synergistically induce endothelial to mesenchymal transition in an NF kappa B-dependent manner

Maleszewska, M., Moonen, J-R. A. J., Huijkman, N., van de Sluis, B., Krenning, G. & Harmsen, M. C., Apr-2013, In : Immunobiology. 218, 4, p. 443-454 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

Endothelial to mesenchymal transition (EndMT) contributes to fibrotic diseases. The main inducer of EndMT is TGF beta signaling. TGF beta 2 is the dominant isoform in the physiological embryonic EndMT, but its role in the pathological EndMT in the context of inflammatory co-stimulation is not known. The aim of this study was to investigate TGF beta 2-induced EndMT in the context of inflammatory IL-1 beta signaling. Co-stimulation with IL-1 beta and TGF beta 2, but not TGF beta 1, caused synergistic induction of EndMT. Also, TGF beta 2 was the only TGF beta isoform that was progressively upregulated during EndMT. External IL-1 beta stimulation was dispensable once EndMT was induced. The inflammatory transcription factor NF kappa B was upregulated in an additive manner by IL-1 beta and TGF beta 2 co-stimulation. Co-stimulation also led to the nuclear translocation of NF kappa B which was sustained over long-term treatment. Activation of NF kappa B was indispensable for the co-induction of EndMT. Our data suggest that the microenvironment at the verge between inflammation (IL-1 beta) and tissue remodeling (TGF beta 2) can strongly promote the process of EndMT. Therefore our findings provide new insights into the mechanisms of pathological EndMT. (C) 2012 Elsevier GmbH. All rights reserved.

Original languageEnglish
Pages (from-to)443-454
Number of pages12
JournalImmunobiology
Volume218
Issue number4
Publication statusPublished - Apr-2013

    Keywords

  • EndMT, IL-1 beta, Inflammation, Fibrosis, NF kappa B, TGF beta 2, GROWTH-FACTOR-BETA, DEVELOPING CHICKEN HEART, SMOOTH-MUSCLE-CELLS, IN-VITRO, VASCULAR ENDOTHELIUM, PROGENITOR CELLS, EMBRYONIC HEART, TRANSFORMATION, EXPRESSION, RECEPTOR

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