title: Light emitting diode-generated blue light modulates fibrosis characteristics: fibroblast proliferation, migration speed, and reactive oxygen species generation.
abstract: OBJECTIVE
  Blue light is part of the visible light spectrum that does not generate harmful DNA adducts associated with skin cancer and photoaging, and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode (LED) red and infrared light inhibits proliferation of skin fibroblasts. Moreover, different wavelengths of light can produce different biological effects. Furthermore, the effects of LED blue light (LED-BL) on human skin fibroblasts are not well characterized. This study investigated the effects of LED-BL on human skin fibroblast proliferation, viability, migration speed, and reactive oxygen-species (ROS) generation.
  
  
  METHODS
  Irradiation of adult human skin fibroblasts using commercially-available LED-BL panels was performed in vitro, and modulation of proliferation and viability was quantified using the trypan blue dye exclusion assay, migratory speed was assessed using time-lapse video microscopy, and intracellular ROS generation was measured using the dihydrorhodamine flow cytometry assay. Statistical differences between groups were determined by ANOVA and Student's t-test.
  
  
  RESULTS
  Human skin fibroblasts treated with LED-BL fluences of 5, 10, 15, 30, and 80 J/cm(2) demonstrated statistically significant dose-dependent decreases in relative proliferation of 8.4%, 29.1%, 33.8%, 51.7%, and 55.1%, respectively, compared to temperature and environment matched bench control plates, respectively. LED-BL fluences of 5, 30, 45, and 80 J/cm(2) decreased fibroblast migration speed to 95 ± 7.0% (P = 0.64), 81.3 ± 5.5% (P = 0.021), 48.5 ± 2.7% (P < 0.0001), and 32.3 ± 1.9% (P < 0.0001), respectively, relative to matched controls. LED fluences of 5, 10, 30, and 80 J/cm(2) resulted in statistically significant increases in reactive oxygen species of 110.4%, 116.6%, 127.5%, and 130%, respectively, relative to bench controls.
  
  
  CONCLUSIONS
  At the fluences studied, LED-BL can inhibit adult human skin dermal fibroblast proliferation and migration speed, and is associated with increased reactive oxygen species generation in a dose-dependent manner without altering viability. LED-BL has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation.
authors: Department of Dermatology, University of California Davis, Sacramento, California; Dermatology Service, Sacramento VA Medical Center, Mather, California.
authors: Andrew
authors: A
authors: Mamalis
authors: Manveer
authors: M
authors: Garcha
authors: Jared
authors: J
authors: Jagdeo
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects*; D005355:Fibrosis; D006801:Humans; D008027:Light; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*
chemical_list: D017382:Reactive Oxygen Species
keywords: Blue LED; fibrosis; light-emitting diode; reactive oxygen species
references: Psychosom Med. 2000 Jul-Aug;62(4):576-82
references: 10949104
references: J Burn Care Rehabil. 2001 Nov-Dec;22(6):401-5
references: 11761392
references: Health Psychol. 2002 Mar;21(2):115-21
references: 11950101
references: J Invest Dermatol. 2002 Dec;119(6):1261-8
references: 12485426
references: BMJ. 2003 Jan 11;326(7380):88-92
references: 12521975
references: J Dermatolog Treat. 2005;16(4):219-23
references: 16249142
references: J Cosmet Laser Ther. 2005 Dec;7(3-4):196-200
references: 16414908
references: Arch Dermatol Res. 2006 Apr;297(10):433-8
references: 16528552
references: J Eur Acad Dermatol Venereol. 2007 May;21(5):643-9
references: 17447978
references: Wound Repair Regen. 2007 Sep-Oct;15 Suppl 1:S32-9
references: 17727465
references: Photochem Photobiol. 2007 Nov-Dec;83(6):1283-300
references: 18028200
references: J Formos Med Assoc. 2008 Jan;107(1):21-9
references: 18218574
references: J Drugs Dermatol. 2008 Feb;7(2 Suppl):s12-6
references: 18404866
references: J Am Acad Dermatol. 2008 May;58(5 Suppl 2):S139-48
references: 18410800
references: J Invest Dermatol. 2010 Aug;130(8):2092-7
references: 20410914
references: J Drugs Dermatol. 2010 Dec;9(12):1523-6
references: 21120261
references: J Photochem Photobiol B. 2011 May 3;103(2):118-25
references: 21421326
references: J Invest Dermatol. 2012 Jul;132(7):1901-7
references: 22318388
references: Dose Response. 2011;9(4):602-18
references: 22461763
references: Br J Dermatol. 2012 Sep;167(3):532-41
references: 22540338
references: Clin Pract Epidemiol Ment Health. 2012;8:30-5
references: 22550545
references: J Invest Dermatol. 2012 Jul;132(7):1756-7
references: 22695285
references: Eur J Dent. 2012 Jul;6(3):311-7
references: 22904660
references: Cell Signal. 2013 Jan;25(1):264-8
references: 23063463
references: Dermatol Surg. 2013 Mar;39(3 Pt 1):422-5
references: 23279196
references: Dermatol Surg. 2013 Aug;39(8):1167-70
references: 23590233
references: J Eur Acad Dermatol Venereol. 2014 Jun;28(6):689-99
references: 24033440
references: PLoS One. 2013 Dec 09;8(12):e75600
references: 24348987
references: Exp Dermatol. 2014 Apr;23(4):240-6
references: 24533842
references: J Trauma. 1983 Nov;23(11):1001-4
references: 6355500
references: J Burn Care Rehabil. 1994 Mar-Apr;15(2):164-8
references: 8195258