IL-17 Signaling Mediates Inflammation-Induced Capillary Leakage in addition to TNFa

Despite its clinical relevance, the mechanisms governing endothelial destabilization under inflammatory conditions remain incompletely understood. In this study, we investigated the endothelial response to inflammation using a dynamic human in vitro model, in which human umbilical vein endothelial cells (HUVECs) were cultured in the presence of lipopolysaccharide (LPS)–stimulated human peripheral blood mononuclear cells (PBMCs) to mimic systemic inflammation.

Under these conditions, endothelial cells exhibited a pronounced inflammatory response characterized by loss of barrier integrity and the formation of capillary leak–like structures. Separated transcriptomic pathway analyses of HUVECs and PBMCs identified a strong activation of cytokine-driven signalling networks, with the IL-17 pathway emerging as a dominant regulator of endothelial dysfunction, alongside TNF and JAK–STAT signalling.