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

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.

Grantor dc:publisher.institution

University of Bradford

Author dc:creator

• Chelmuș, Alina

Advisors dc:contributor.advisor

• Thornton, M. Julie
• Riches-Suman, Kirsten

• Wound healing
• Soluble IL-6Rα receptor
• Adipose-derived stem cells
• Dermal fibroblasts
• Migration
• IL-6 trans-signalling pathway
• Interleukin-6 (IL-6)

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://bradscholars.brad.ac.uk/handle/10454/20543

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/20543