Open Access

ARTICLE

Cyclic Stretch Induces Inflammatory Cytokines via the Oxidative Stress and NF-ΚB Pathways Activation in Human Keratoconic Fibroblasts

by Xiaona Li^1,*, Sijia Wang¹, Jie Song¹, Yixian Qin², Jizhong Yang³, Rui He^4,*, Weiyi Chen¹

1 College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
2 Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794 5281, USA
3 Keratonosus Department, Shanxi Eye Hospital, Taiyuan, 030002, China
4 Excimer Laser Department, Shanxi Eye Hospital, Taiyuan, 030002, China

* Corresponding Authors: Xiaona Li. Email: ; Rui He. Email:

Molecular & Cellular Biomechanics 2021, 18(1), 11-19. https://doi.org/10.32604/mcb.2021.014071

Received 02 September 2020; Accepted 17 November 2020; Issue published 26 January 2021

Abstract

The cornea is a load-bearing tissue. Lower biomechanical properties in the local tissue of keratoconic cornea evoke mechanical stress increase. Inflammatory cytokines have been shown to be over-expressed in patients with keratoconus. However, how mechanical stimuli are involved in the production of inflammatory cytokines in keratoconus remains unclear. The objective of the study is to determine the role of mechanical stretch in the regulation of inflammatory cytokines and the underlying mechanisms in keratoconus. Human keratoconic fibroblasts (hKCFs) were subjected to 12% cyclic mechanical stretch at 0.1 Hz or in static conditions as controls. N-acetyl cysteine (NAC) and pyrrolidine dithiocarbamate and pyrrolidine dithiocarbamate (PDTC) were used to inhibit reactive oxygen species (ROS) production and NF-κB pathway respectively. ROS production was measured using 2’,7’-dichlorodihydrofluorescindiacetate probe. Conditioned media and cell lysates were collected for protein assessment. Cyclic stretch-induced a higher production of intercellular cell adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-8 in hKCFs than static controls. ROS was also elevated in response to cyclic stretch. Inhibition of ROS or NF-κB attenuated stretch-induced ICAM-1, TNF-α, IL-6, and IL-8. Inhibition of stretch-induced ROS production by NAC also attenuated NF-κB activation. Our findings suggest that mechanical stretch may induce the release of inflammatory cytokines by activating oxidative stress and NF-kB pathway, and ROS may positively control NF-κB signaling. Over-expression of inflammatory cytokines induced by mechanical stretch may play a role in progression of keratoconus.

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