Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration

Mamalis, Andrew; Koo, Eugene; Isseroff, Roslyn Rivkah; Murphy, William J.; Jagdeo, Jared

doi:10.1371/journal.pone.0140628

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…Our group recently found that LED-RL increased ROS levels and decreased fibroblast migration speed in a dose-dependent manner (Fig. 3 ) [ 35 ••]. Additionally, we found that LED-RL also altered phospho-Akt levels (unpublished data by Jagdeo Lab).…”

Section: Effects Of Red Light On Cellular Functions Related To Fibrossupporting

confidence: 68%

“…Our group has found that LED-RL is capable of inhibiting fibroblast proliferation in a dose-dependent manner [ 34 ]. Furthermore, red light does not appear to affect fibroblast viability, with no increases in apoptosis or necrosis observed [ 34 , 35 ••]. This suggests that visible red light is likely modulating fibroblast function through means other than direct cellular cytotoxicity, such as through modulation of the cell cycle or autophagy.…”

Section: Effects Of Red Light On Cellular Functions Related To Fibrosmentioning

confidence: 99%

“…It is likely that these alterations in proliferation are a result of alterations in the redox state of fibroblasts treated with LED-RL. While mild elevations in free radicals have been shown to increase proliferation, we have found that the dose-dependent decreases in fibroblast proliferation are associated with a dose-dependent sustained increase in ROS [ 35 ••, 36 ]. Therefore, it is likely that the sustained alterations in the redox state of fibroblasts treated with LED-RL and the subsequent redox-initiated alterations in the TGF-beta pathway and related pathways are contributing to the dose-dependent decrease in fibroblast proliferation.…”

Section: Effects Of Red Light On Cellular Functions Related To Fibrosmentioning

confidence: 99%

“…Additionally, we found that LED-RL also altered phospho-Akt levels (unpublished data by Jagdeo Lab). Furthermore, migration speed returned to control levels when ROS increases were blocked by the pretreatment of fibroblasts with the antioxidant resveratrol or when cells were pretreated with the PI3K/Akt inhibitor LY294002 [ 35 ••]. This suggests that LED-RL’s effects on migration may be largely mediated by increased ROS that lead to modulation of phospho-Akt levels and subsequent alterations in fibroblast migration speed.…”

Section: Effects Of Red Light On Cellular Functions Related To Fibrosmentioning

confidence: 99%

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Visible Red Light Emitting Diode Photobiomodulation for Skin Fibrosis: Key Molecular Pathways

2016

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Skin fibrosis, also known as skin scarring, is an important global health problem that affects an estimated 100 million persons per year worldwide. Current therapies are associated with significant side effects and even with combination therapy, progression, and recurrence is common. Our goal is to review the available published data available on light-emitting diode-generated (LED) red light phototherapy for treatment of skin fibrosis. A search of the published literature from 1 January 2000 to present on the effects of visible red light on skin fibrosis, and related pathways was performed in January 2016. A search of PubMed and EMBASE was completed using specific keywords and MeSH terms. “Fibrosis” OR “skin fibrosis” OR “collagen” was combined with (“light emitting diode,” “LED,” “laser,” or “red light”). The articles that were original research studies investigating the use of visible red light to treat skin fibrosis or related pathways were selected for inclusion. Our systematic search returned a total of 1376 articles. Duplicate articles were removed resulting in 1189 unique articles, and 133 non-English articles were excluded. From these articles, we identified six articles related to LED effects on skin fibrosis and dermal fibroblasts. We augmented our discussion with additional in vitro data on related pathways. LED phototherapy is an emerging therapeutic modality for treatment of skin fibrosis. There is a growing body of evidence demonstrating that visible LED light, especially in the red spectrum, is capable of modulating key cellular characteristic associated with skin fibrosis. We anticipate that as the understanding of LED-RL’s biochemical mechanisms and clinical effects continue to advance, additional therapeutic targets in related pathways may emerge. We believe that the use of LED-RL, in combination with existing and new therapies, has the potential to alter the current treatment paradigm of skin fibrosis. There is a current lack of clinical trials investigating the efficacy of LED-RL to treat skin fibrosis. Randomized clinical trials are needed to demonstrate visible red light’s clinical efficacy on different types of skin fibrosis.

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Section: Effects Of Red Light On Cellular Functions Related To Fibrossupporting

confidence: 68%

Section: Effects Of Red Light On Cellular Functions Related To Fibrosmentioning

confidence: 99%

Section: Effects Of Red Light On Cellular Functions Related To Fibrosmentioning

confidence: 99%

Section: Effects Of Red Light On Cellular Functions Related To Fibrosmentioning

confidence: 99%

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Visible Red Light Emitting Diode Photobiomodulation for Skin Fibrosis: Key Molecular Pathways

2016

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“…We hypothesize that these increases in ROS may play a role in initiating the photobiomodulatory effects of HF‐LED‐RL and further investigation is warranted. We recently demonstrated that the antioxidant resveratrol is capable of preventing the photobiomodulatory effects of HF‐LED‐RL on HDF migration .…”

Section: Discussionmentioning

confidence: 97%

High fluence light emitting diode‐generated red light modulates characteristics associated with skin fibrosis

Mamalis

Koo

Garcha

et al. 2016

Journal of Biophotonics

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Skin fibrosis, often referred to as skin scarring, is a significant international health problem with limited treatment options. The hallmarks of skin fibrosis are increased fibroblast proliferation, collagen production, and migration speed. Recently published clinical observations indicate that visible red light may improve skin fibrosis. In this study we hypothesize that high-fluence light-emitting diode-generated red light (HF-LED-RL) modulates the key cellular features of skin fibrosis by decreasing cellular proliferation, collagen production, and migration speed of human skin fibroblasts. Herein, we demonstrate that HF-LED-RL increases reactive oxygen species (ROS) generation for up to 4 hours, inhibits fibroblast proliferation without increasing apoptosis, inhibits collagen production, and inhibits migration speed through modulation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. We demonstrate that HF-LED-RL is capable of inhibiting the unifying cellular processes involved in skin fibrosis including fibroblast proliferation, collagen production, and migration speed. These findings suggest that HF-LED-RL may represent a new approach to treat skin fibrosis. LED advantages include low cost, portability, and ease of use. Further characterizing the photobiomodulatory effects of HF-LED-RL on fibroblasts and investigating the anti-fibrotic effects of HF-LED-RL in human subjects may provide new insight into the utility of this therapeutic approach for skin fibrosis.

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Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice

et al. 2017

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Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm, irradiance 33.3 mW/cm, spot size 2.8cm, total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.

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Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration

Cited by 9 publications

References 21 publications

Visible Red Light Emitting Diode Photobiomodulation for Skin Fibrosis: Key Molecular Pathways

Visible Red Light Emitting Diode Photobiomodulation for Skin Fibrosis: Key Molecular Pathways

High fluence light emitting diode‐generated red light modulates characteristics associated with skin fibrosis

Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice

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