Low-Power Laser Irradiation Suppresses Inflammatory Response of Human Adipose-Derived Stem Cells by Modulating Intracellular Cyclic AMP Level and NF-κB Activity

Mesenchymal stem cell (MSC)-based tissue regeneration is a promising therapeutic strategy for treating damaged tissues. However, the inflammatory microenvironment that exists at a local injury site might restrict reconstruction. Low-power laser irradiation (LPLI) has been widely applied to retard the inflammatory reaction. The purpose of this study was to investigate the anti-inflammatory effect of LPLI on human adipose-derived stem cells (hADSCs) in an inflammatory environment. We showed that the hADSCs expressed Toll-like Receptors (TLR) 1, TLR2, TLR3, TLR4, and TLR6 and that lipopolysaccharide (LPS) significantly induced the production of pro-inflammatory cytokines (Cyclooxygenase-2 (Cox-2), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Interleukin-8 (IL-8)). LPLI markedly inhibited LPS-induced, pro-inflammatory cytokine expression at an optimal dose of 8 J/cm2. The inhibitory effect triggered by LPLI might occur through an increase in the intracellular level of cyclic AMP (cAMP), which acts to down-regulate nuclear factor kappa B (NF-κB) transcriptional activity. These data collectively provide insight for further investigations of the potential application of anti-inflammatory treatment followed by stem cell therapy.

[1]  R. Medzhitov,et al.  TIRAP: an adapter molecule in the Toll signaling pathway , 2001, Nature Immunology.

[2]  Meijing Wang,et al.  STEM CELL MECHANISMS AND PARACRINE EFFECTS: POTENTIAL IN CARDIAC SURGERY , 2007, Shock.

[3]  N. Mackman,et al.  Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription. , 1997, Journal of immunology.

[4]  H. Erdjument-Bromage,et al.  The Transcriptional Activity of NF-κB Is Regulated by the IκB-Associated PKAc Subunit through a Cyclic AMP–Independent Mechanism , 1997, Cell.

[5]  H. Erdjument-Bromage,et al.  The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism. , 1997, Cell.

[6]  R. Albertini,et al.  Low level laser therapy modulates kinin receptors mRNA expression in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation. , 2008, International immunopharmacology.

[7]  A. Zapata,et al.  Mesenchymal stem cells: biological properties and clinical applications , 2010, Expert opinion on biological therapy.

[8]  S. Mckercher,et al.  Wound Healing in the PU.1 Null Mouse—Tissue Repair Is Not Dependent on Inflammatory Cells , 2003, Current Biology.

[9]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[10]  Shizuo Akira,et al.  Toll-like receptor signalling , 2004, Nature Reviews Immunology.

[11]  James M. Anderson,et al.  Foreign body reaction to biomaterials. , 2008, Seminars in immunology.

[12]  V. Iversen,et al.  Low-level laser therapy (GaAs lambda = 904 nm) reduces inflammatory cell migration in mice with lipopolysaccharide-induced peritonitis. , 2007, Photomedicine and laser surgery.

[13]  A. Bowie,et al.  The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling , 2007, Nature Reviews Immunology.

[14]  E. Lombardo,et al.  Toll-like receptor-mediated signaling in human adipose-derived stem cells: implications for immunogenicity and immunosuppressive potential. , 2009, Tissue engineering. Part A.

[15]  R. Albertini,et al.  Low Level Laser Therapy (LLLT) Decreases Pulmonary Microvascular Leakage, Neutrophil Influx and IL-1β Levels in Airway and Lung from Rat Subjected to LPS-Induced Inflammation , 2008, Inflammation.

[16]  A. Caplan.  Adult mesenchymal stem cells for tissue engineering versus regenerative medicine , 2007, Journal of cellular physiology.

[17]  Leonardo M. Moreira,et al.  Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome , 2011, Lasers in Medical Science.

[18]  D. K. Arrell,et al.  Cardiopoietic programming of embryonic stem cells for tumor-free heart repair , 2007, The Journal of experimental medicine.

[19]  G. Haegeman,et al.  Cyclic AMP: a selective modulator of NF-κB action , 2011, Cellular and Molecular Life Sciences.

[20]  J. González‐Gallego,et al.  Effects of low‐level laser therapy (LLLT) on the nuclear factor (NF)‐κB signaling pathway in traumatized muscle , 2006, Lasers in surgery and medicine.

[21]  C. E. Leite,et al.  Anti‐Inflammatory effects of low‐level laser therapy (660 nm) in the early phase in carrageenan‐induced pleurisy in rat , 2008, Lasers in surgery and medicine.

[22]  U. Gether.  Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. , 2000, Endocrine reviews.

[23]  L. O’Neill,et al.  Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. , 2006, Biochemical pharmacology.

[24]  Bindiya Patel,et al.  Adipose-derived stem cells: isolation, expansion and differentiation. , 2008, Methods.

[25]  M. Ashraf,et al.  Bone Marrow Stem Cells Prevent Left Ventricular Remodeling of Ischemic Heart Through Paracrine Signaling , 2006, Circulation research.

[26]  R. Albertini,et al.  Low-level laser therapy decreases levels of lung neutrophils anti-apoptotic factors by a NF-kappaB dependent mechanism. , 2008, International immunopharmacology.

[27]  Y Abiko,et al.  Inhibitory effect of low-level laser irradiation on LPS-stimulated prostaglandin E2 production and cyclooxygenase-2 in human gingival fibroblasts. , 2000, European journal of oral sciences.

[28]  R. Albertini,et al.  Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase-induced tendinitis in rat , 2010, Lasers in Medical Science.

[29]  Y. Bae,et al.  Role of Toll‐Like Receptors on Human Adipose‐Derived Stromal Cells , 2006, Stem cells.

[30]  D. Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986. 46: 705-716. , 2006, Journal of immunology.

[31]  Z. Cui,et al.  Adipose-derived stem cell: A better stem cell than BMSC , 2008, Cell Research.

[32]  Heidi Abrahamse,et al.  Mitochondrial Responses of Normal and Injured Human Skin Fibroblasts Following Low Level Laser Irradiation—An In Vitro Study , 2009, Photochemistry and photobiology.

[33]  Jyun-Yi Wu,et al.  Low-Power GaAlAs Laser Irradiation Promotes the Proliferation and Osteogenic Differentiation of Stem Cells via IGF1 and BMP2 , 2012, PloS one.