Modulation of angiogenesis by inflammatory markers and the role of matrix metalloproteinases in an endothelial cell/fibroblast co-culture system.

Barron, Gemma A.; Bordet, Elise; Goua, Marie; Bermano, Giovanna

Abstract

Increased levels of inflammatory markers such as tumour necrosis factor-α (TNFα) and interleukin- 6 (IL-6) have been associated with formation of new blood vessels, or angiogenesis, and linked to chronic inflammation in obesity. This study aimed to establish and use a versatile co-culture cell system to further investigate the role of TNFα and IL-6 in modulating (i) tubule formation and (ii) cell-cell interactions via matrix metalloproteinase (MMP) enzyme activity and secretion of vascular endothelial growth factor (VEGF), E-selectin and prostaglandin E2 (PGE2). Co-cultures of human endothelial cells and fibroblasts were incubated with TNFα (10 ng/mL) or IL-6 (10 ng/mL) added 2 and/or 7 days after co-culture establishment. Cell viability by enzymatic conversion was determined by MTT assay; tubule formation was detected by immunostaining; VEGF, E-selectin and PGE2 expression by ELISA analysis and MMP enzyme activity by gel zymography. Treatmentspecific and time dependent differences in tubule formation were observed: IL-6 significantly increased tubule formation, whilst TNFα significantly inhibited tubule formation. Treatment-specific differences in levels of MMP activities which correlate to tubule formation were also observed. This study showed inflammatory markers, typically associated with obese status, affect tubule formation differently in a heterogeneous cell environment similar to that observed in vivo.

Citation

BARRON, G.A., BORDET, E., GOUA, M. and BERMANO. G. 2014. Modulation of angiogenesis by inflammatory markers and the role of matrix metalloproteinases in an endothelial cell/fibroblast co-culture system. Current angiogenesis [online], 3(3), pages 152-163. Available from: https://doi.org/10.2174/2211552803666141113211829

• Journal Article Type: Article
• Acceptance Date: Nov 14, 2014
• Online Publication Date: Dec 31, 2014
• Publication Date: Mar 11, 2015
• Deposit Date: Feb 18, 2020
• Publicly Available Date: Feb 18, 2020
• Journal: Current angiogenesis
• Print ISSN: 2211-5528
• Electronic ISSN: 2211-5536
• Publisher: Bentham Open
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 3
• Pages: 152-163
• DOI: https://doi.org/10.2174/2211552803666141113211829
• Keywords: Angiogenesis; Co-culture; Cytokines; Fibroblasts; HUVEC; Obesity
• Public URL: https://rgu-repository.worktribe.com/output/828477