Adult stem cells are tissue resident and thus affected by local injury, infection and inflammation. However, the impact of pro- and anti-inflammatory signalling on stem cells is not fully understood. In particular, inflammation seems to have different effects on proliferation, differentiation and migration of stem cells depending on the origin of the cell (tissue and species), the developmental context (embryonic vs adult) and the duration of the exposure to the signal (acute vs. chronic inflammation).

Here, we are mainly interested in the signalling cascaded mediated by the Toll-like Receptor 4 (TLR4) and Tumor Necrosis Factor Receptor 1 (TNF-R1). Notably, while stimulation of TNF-R1 leads to activation of pro-inflammatory signalling, ligation of TLR4 culminates in both: pro- and anti-inflammatory signal transduction.

Fig. 1. Activation of TLR4 can culminate in pro- and anti-inflammatory signalling. In contrast, binding of Tumor Necrosis Factor-alpha to TNF-R1 exclusively activates pro-inflammatory signalling mainly mediated by the transcription factor NF-kappaB.

We want to understand how the inflammatory balance and manipulation thereof influences differentiation, proliferation and migration of stem cells, including neural stem cells, mesenchymal stem cells and neural crest-derived stem cells. We use modern microscopy in addition to biochemical methods to understand the respective signal transduction pathways at the level of receptors and the downstream signalling events.

Fig. 2. Treatment of U251 model cell line with the TLR4-ligand LPS leads to nuclear translocation of the pro-inflammatory transcription factor NF-kappaB as visualized using antibodies against its subunit p65.

Our work on TLR4 is a collaboration with Prof. Mike Heilemann (Institute for Physical and Theoretical Chemistry Goethe-University Frankfurt, Germany) and is funded by the German Research Council DFG (WI4318/2-1).



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