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-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

Monte Carlo study of LSO gamma-ray detectors for PET.

We have made a detailed study of the response of LSO detectors to 511 keV gamma-rays. The LSO, discovered recently, has a density greater than EGO, small decay time, and high light output. As such, it should have an overall behavior better than that of EGO. We have modeled a gamma-ray detector using an LSO crystal of rectangular cross-section attached to a photomultiplier tube (PMT). We used our PET simulation package to study the energy resolution, efficiency, and timing resolution for various crystal sizes and various energy thresholds. The simulation takes into account the interactions of gamma-rays in the crystal via Compton and photoelectric effects, the production and transport of scintillation photons, the productions of photoelectrons in the PMT and the anode signal formation. We have estimated the efficiency versus energy threshold for various lengths of the LSO crystal and we find that for 400 keV threshold this efficiency is large even for 2 cm crystals and comparable to that of EGO. We also estimated the timing resolution (FWHM) versus crystal length for various energy thresholds. The timing resolution is comparable to that of CeF3 detectors. The energy resolution is about 10 % (FWHM), which allows one to set the energy threshold fairly high