Low-level laser therapy prevents endothelial cells from TNF-α/cycloheximide-induced apoptosis

• Published in: Lasers in medical science Vol. 33; no. 2; pp. 279 - 286
• Main Authors: Chu, Yu-Hsiu, Chen, Shu-Ya, Hsieh, Yueh-Ling, Teng, Yi-Hsien, Cheng, Yu-Jung
• Format: Journal Article
• Language: English
• Published: London Springer London 01.02.2018; Springer Nature B.V
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Caspase; Caspase 3 - metabolism; Caspase-3; Cell death; Cell growth; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Cell Survival - drug effects; Cell Survival - radiation effects; Cycloheximide; Cycloheximide - adverse effects; Dentistry; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - pathology; Endothelial Cells - radiation effects; Enzyme Activation - drug effects; Enzyme Activation - radiation effects; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblasts; Humans; Inflammation; JNK protein; Kinases; Lasers; Levels; Low-Level Light Therapy; MAP kinase; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - radiation effects; Medicine; Medicine & Public Health; Molecular modelling; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Optical Devices; Optics; Original Article; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Phosphorylation - radiation effects; Photonics; Physical therapy; Protein kinase; Quantum Optics; Signaling; Translocation; Tumor Necrosis Factor-alpha - adverse effects; Tumor necrosis factor-α; Wound healing; Inflammation; LLLT; Caspases; TNF-α; MAPK; Apoptosis
• ISSN: 0268-8921; 1435-604X
• DOI: 10.1007/s10103-017-2364-x

Low-level laser therapy (LLLT), widely used in physiotherapy, has been known to enhance wound healing and stimulate cell proliferation, including fibroblast and endothelial cells. Applying LLLT can increase cell proliferation in many kinds of cells including fibroblasts and endothelial cells. However, the protective mechanisms of LLLT on endothelial apoptosis remain unclear. We hypothesized LLLT can protect endothelial cells from inflammation-induced apoptosis. Human endothelial cell line, EA.hy926 cells, and TNF-α/cycloheximide (TNF/CHX) were used to explore the protective effects of LLLT (660 nm) on inflammation-induced endothelial apoptosis. Cell viability, apoptosis, caspase-3/7/8/9 activity, MAPKs signaling, NF-κB activity, and inducible/endothelial nitric oxide synthase (iNOS/eNOS) expression were measured. Our results showed that LLLT increased EA.hy926 cell proliferation, attenuated the TNF/CHX-induced apoptosis, and reduced the TNF/CHX-mediated caspase-3/7/8/9 activation. In addition, LLLT increased ERK MAPK phosphorylation and suppressed the TNF/CHX-increased p38 MAPK, JNK, IKK phosphorylation, NF-κB translocation, and iNOS expression. The caspases-3 cleavage and cell death were not increased in cells treating with ERK inhibitor U0126, which implicated that ERK is not to be responsible for the protective effects of LLLT. After treating with p38 mitogen-activated protein kinase (MAPK) activator, the protection of LLLT in cell apoptosis was no longer existed, showing that LLLT protected the endothelial cells by suppressing p38 MAPK signaling. Our results provide a new insight into the possible molecular mechanisms in which LLLT protects against inflammatory-induced endothelial dysfunction.