Modulation of human adipose-derived stem cells and dermal fibroblasts in co-cultures by activation of the IL-6 trans-signalling pathway via the soluble IL-6Rα receptor
Chelmuș, Alina
Chelmuș, Alina
Publication Date
End of Embargo
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The University of Bradford theses are licenced under a Creative Commons Licence.
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Accepted for publication
Institution
University of Bradford
Department
School of Chemistry and Biosciences. Faculty of Life Sciences
Awarded
2023
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Abstract
Interleukin-6 (IL-6), a major wound healing cytokine, has rare, versatile agonistic effects, due to dual pro and anti-inflammatory roles depending on the intracellular signalling pathway.
The aim was to evaluate the relationship between human dermal fibroblasts (DF), human adipose-derived stem cells (ADSC), IL-6 and activation of the IL-6 trans-signalling pathway under four different cell culture conditions.
The two cell types were co-cultured to assess cell migration when pre-treated with the soluble human IL-6Rα receptor (rhIL-6Rα). In addition, secreted cytokine levels (TGFβ1, TGFβ3 and VEGF) and biomarker expression (TGF β1RII, SMAD2/3, SMAD 1/5/9 and SMA) were quantitated.
Although both cell types secreted IL-6, ADSC basal levels were 100-fold that of DF. Both cell types expressed CD130 (gp130) signalling transductor but were negative for the membrane-bound CD126 receptor required for the classical IL-6 signalling pathway.
Following IL-6 trans-signalling pathway activation with rhIL-6Rα, ADSC migrated predominantly, while DF acted more as attractants. Moreover, the overall secretion of TGFβ3 and VEGF, and the ratio of TGFβ3/TGFβ1 showed similar variations which suggested they increased, although not statistically significant and were maintained at 72h, but only in co-cultures where the ADSC were pre-treated. When cells were pre-treated with rhIL-6Rα, the overall expression of TGFβRII and SMAD2/3 increased suggesting crosstalk between TGFβ1 and IL-6.
In summary, these results suggest that activation of the IL-6 trans-signalling pathway modulates ADSC plasticity impacting on migration. Thus, further research is required to assess the use of ADSC in concurrence with manipulation of the IL-6 signalling pathway in wound management.
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Thesis
Qualification name
MPhil