title: Combined effects of substrate topography and stiffness on endothelial cytokine and chemokine secretion.
abstract: Endothelial physiology is regulated not only by humoral factors, but also by mechanical factors such as fluid shear stress and the underlying cellular matrix microenvironment. The purpose of the present study was to examine the effects of matrix topographical cues on the endothelial secretion of cytokines/chemokines in vitro. Human endothelial cells were cultured on nanopatterned polymeric substrates with different ratios of ridge to groove widths (1:1, 1:2, and 1:5) and with different stiffnesses (6.7 MPa and 2.5 GPa) in the presence and absence of 1.0 ng/mL TNF-α. The levels of cytokines/chemokines secreted into the conditioned media were analyzed with a multiplexed bead-based sandwich immunoassay. Of the nanopatterns tested, the 1:1 and 1:2 type patterns were found to induce the greatest degree of endothelial cell elongation and directional alignment. The 1:2 type nanopatterns lowered the secretion of inflammatory cytokines such as IL-1β, IL-3, and MCP-1, compared to unpatterned substrates. Additionally, of the two polymers tested, it was found that the stiffer substrate resulted in significant decreases in the secretion of IL-3 and MCP-1. These results suggest that substrates with specific extracellular nanotopographical cues or stiffnesses may provide anti-atherogenic effects like those seen with laminar shear stresses by suppressing the endothelial secretion of cytokines and chemokines involved in vascular inflammation and remodeling.
authors: Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422, Republic of Korea.
authors: Hyeona
authors: H
authors: Jeon
authors: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors: Jonathan H
authors: JH
authors: Tsui
authors: Cell and Matrix Research Institute, Kyungpook National University, Daegu, 700-422, Republic of Korea.
authors: Sue Im
authors: SI
authors: Jang
authors: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors: Justin H
authors: JH
authors: Lee
authors: Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422, Republic of Korea.
authors: Soojin
authors: S
authors: Park
authors: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors: Kevin
authors: K
authors: Mun
authors: Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422, Republic of Korea.|Cell and Matrix Research Institute, Kyungpook National University, Daegu, 700-422, Republic of Korea.
authors: Yong Chool
authors: YC
authors: Boo
authors: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.|Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA.
authors: Deok-Ho
authors: DH
authors: Kim
mesh_terms: D002460:Cell Line; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry
chemical_list: D018925:Chemokines; D016207:Cytokines; D011108:Polymers
keywords: chemokines; cytokines; endothelial cells; nanotopography; substrate stiffness