Evaluation of NFκB-dependent inflammatory responses induced by TNFα in 3D human microvessels
6
Issued Date
2025-05-01
Resource Type
eISSN
24058440
Scopus ID
2-s2.0-105005115838
Journal Title
Heliyon
Volume
11
Issue
10
Rights Holder(s)
SCOPUS
Bibliographic Citation
Heliyon Vol.11 No.10 (2025)
Suggested Citation
Den-Udom T., Asavapanumas N., Bunyapraphatsara N., Muta K., Ketsawatsomkron P. Evaluation of NFκB-dependent inflammatory responses induced by TNFα in 3D human microvessels. Heliyon Vol.11 No.10 (2025). doi:10.1016/j.heliyon.2025.e43397 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110304
Title
Evaluation of NFκB-dependent inflammatory responses induced by TNFα in 3D human microvessels
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Abstract
Endothelial inflammation underlies the development of cardiovascular complications. Recently, advances in three-dimensional (3D) in vitro models that recapitulate human microvessel functions have been increasingly described. However, the pathological mechanisms of endothelial cells (ECs) in 3D microvessels remain to be elucidated. Here, we examined the involvement of nuclear factor κB (NFκB) in vascular inflammation of 3D microvessels. Human umbilical vein ECs were cultured in a microfluidic device (OrganoPlate) under luminal flow. 3D microvessels were highly stable and exhibited tubular structures with low permeability to different sized macromolecules. Tumor necrosis factor (TNF) α stimulation increased vascular leakage, which was associated with disruption of VE-cadherin and F-actin. Moreover, marked induction of monocyte adhesion, VCAM-1, and IL-6 was observed following TNFα treatment in the 3D microvessels. These effects of TNFα were significantly abrogated by pretreatment of microvessels with NFκB inhibitor, BAY 11–7082. TNFα also increased nuclear translocation of NFκB p65 in endothelial tubes, which was partially blunted by BAY 11–7082. We concluded that NFκB signaling remained intact and drove the inflammatory responses to TNFα in 3D microvessels. Our study demonstrates the feasibility of using a 3D platform to investigate inflammation-related pathogenesis of microvasculature diseases in a more physiological context.