Low-level laser therapy attenuates lung inflammation and airway remodeling in a murine model of idiopathic pulmonary fibrosis: Relevance to cytokines secretion from lung structural cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic inflammatory disease with a poor prognosis and very few available treatment options. Low-level laser therapy (LLLT) has been gaining prominence as a new and effective anti-inflammatory and immunomodulatory agent. Can lung inflammation and the airway remodeling be regulated by LLLT in an experimental model of IPF in C57Bl/6 mice? The present study investigated if laser attenuates cellular migration to the lungs, the airway remodeling as well as pro-fibrotic cytokines secretion from type II pneumocytes and fibroblasts. Mice were irradiated (780 nm and 30 mW) and then euthanized fifteen days after bleomycin-induced lung fibrosis. Lung inflammation and airway remodeling were evaluated through leukocyte counting in bronchoalveolar lavage fluid (BALF) and analysis of collagen in lung, respectively. Inflammatory cells in blood were also measured. For in vitro assays, bleomycin-activated fibroblasts and type II pneumocytes were irradiated with laser. The pro- and anti-inflammatory cytokines level in BALF as well as cells supernatant were measured by ELISA, and the TGFß in lung was evaluated by flow cytometry. Lung histology was used to analyze collagen fibers around the airways. LLLT reduced both migration of inflammatory cells and deposition of collagen fibers in the lungs. In addition, LLLT downregulated pro-inflammatory cytokines and upregulated the IL-10 secretion from fibroblasts and pneumocytes. Laser therapy greatly reduced total lung TGFß. Systemically, LLLT also reduced the inflammatory cells counted in blood. There is no statistical difference in inflammatory parameters studied between mice of the basal group and the laser-treated mice. Data obtained indicate that laser effectively attenuates the lung inflammation, and the airway remodeling in experimental pulmonary fibrosis is driven to restore the balance between the pro- and anti-inflammatory cytokines in lung and inhibit the pro-fibrotic cytokines secretion from fibroblasts.

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1ß, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.