Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts
Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/66163 |
| _version_ | 1826216398336032768 |
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| author | Chen, Aaron Chih-Hao Arany, Praveen R. Huang, Ying-Ying Tomkinson, Elizabeth M. Sharma, Sulbha K. Kharkwal, Gitika B. Saleem, Taimur Mooney, David J. Yull, Fiona E. Blackwell, Timothy S. Hamblin, Michael R. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Chen, Aaron Chih-Hao Arany, Praveen R. Huang, Ying-Ying Tomkinson, Elizabeth M. Sharma, Sulbha K. Kharkwal, Gitika B. Saleem, Taimur Mooney, David J. Yull, Fiona E. Blackwell, Timothy S. Hamblin, Michael R. |
| author_sort | Chen, Aaron Chih-Hao |
| collection | MIT |
| description | Background
Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear.
Methodology/Principal Findings
In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration.
Conclusion
We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT. |
| first_indexed | 2024-09-23T16:47:00Z |
| format | Article |
| id | mit-1721.1/66163 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:47:00Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/661632022-09-29T21:26:29Z Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts Chen, Aaron Chih-Hao Arany, Praveen R. Huang, Ying-Ying Tomkinson, Elizabeth M. Sharma, Sulbha K. Kharkwal, Gitika B. Saleem, Taimur Mooney, David J. Yull, Fiona E. Blackwell, Timothy S. Hamblin, Michael R. Harvard University--MIT Division of Health Sciences and Technology Hamblin, Michael R. Hamblin, Michael R. Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT. National Institutes of Health (U.S.) (grant R01AI050875) Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006) United States. Dept. of Defense (CDMRP Program in TBI, W81XWH-09-1-0514) United States. Air Force Office of Scientific Research (FA9950-04-1-0079) 2011-10-03T17:34:16Z 2011-10-03T17:34:16Z 2011-07 2011-02 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/66163 Chen, Aaron C-H. et al. “Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts.” Ed. Wafik S. El-Deiry. PLoS ONE 6 (2011): e22453. en_US http://dx.doi.org/10.1371/journal.pone.0022453 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Chen, Aaron Chih-Hao Arany, Praveen R. Huang, Ying-Ying Tomkinson, Elizabeth M. Sharma, Sulbha K. Kharkwal, Gitika B. Saleem, Taimur Mooney, David J. Yull, Fiona E. Blackwell, Timothy S. Hamblin, Michael R. Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts |
| title | Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts |
| title_full | Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts |
| title_fullStr | Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts |
| title_full_unstemmed | Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts |
| title_short | Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts |
| title_sort | low level laser therapy activates nf kb via generation of reactive oxygen species in mouse embryonic fibroblasts |
| url | http://hdl.handle.net/1721.1/66163 |
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