Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor

Gabriel da Cunha Moraes, Luana Beatriz Vitoretti, Auriléia Aparecida de Brito, Cintia Estefano Alves, Nicole Cristine Rigonato de Oliveira, Alana Dos Santos Dias, Yves Silva Teles Matos, Manoel Carneiro Oliveira-Junior, Luis Vicente Franco Oliveira, Renata Kelly da Palma, Larissa Carbonera Candeo, Adriana Lino-Dos-Santos-Franco, Anna Carolina Ratto Tempestine Horliana, João Antonio Gimenes Júnior, Flavio Aimbire, Rodolfo Paula Vieira, Ana Paula Ligeiro-de-Oliveira, Gabriel da Cunha Moraes, Luana Beatriz Vitoretti, Auriléia Aparecida de Brito, Cintia Estefano Alves, Nicole Cristine Rigonato de Oliveira, Alana Dos Santos Dias, Yves Silva Teles Matos, Manoel Carneiro Oliveira-Junior, Luis Vicente Franco Oliveira, Renata Kelly da Palma, Larissa Carbonera Candeo, Adriana Lino-Dos-Santos-Franco, Anna Carolina Ratto Tempestine Horliana, João Antonio Gimenes Júnior, Flavio Aimbire, Rodolfo Paula Vieira, Ana Paula Ligeiro-de-Oliveira

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT) is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD. C57BL/6 mice were submitted to cigarette smoke for 75 days (2x/day). After 60 days to smoke exposure, the treated group was submitted to LLLT (diode laser, 660 nm, 30 mW, and 3 J/cm2) for 15 days and euthanized for morphologic and functional analysis of the lungs. Our results showed that LLLT significantly reduced the number of inflammatory cells and the proinflammatory cytokine secretion such as IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF). We also observed that LLLT decreased collagen deposition as well as the expression of purinergic P2X7 receptor. On the other hand, LLLT increased the IL-10 release. Thus, LLLT can be pointed as a promising therapeutic approach for lung inflammatory diseases as COPD.

Figures

Figure 1
Figure 1
Treatment with LLL reduces cellular infiltration in BALF of COPD animals. Quantification of total cells (a), macrophages (b), neutrophils (c), and lymphocytes (d) in bronchoalveolar lavage fluid. Data are expressed as mean ± SD of three independent experiments. n = 5–8 animals per group. ∗P < 0.05 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.
Figure 2
Figure 2
Treatment with LLL reduces mononuclear and polymorphonuclear cells in peribronchial space of COPD animals. Quantification of mononuclear (a) and polymorphonuclear (b) cells in peribronchial space in lung parenchyma. Data are expressed as mean ± SD of three independent experiments. n = 5–8 animals per group. ∗P < 0.05 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.
Figure 3
Figure 3
Treatment with LLL reduces proinflammatory cytokine secretion and increases the levels of IL-10 in the BALF of COPD animals. Quantification of IL-6 (a), IL-1β (b), IL-17 (c), TNF-α (d), KC (e), and IL-10 (f) in bronchoalveolar lavage fluid supernatants. Data are expressed as mean ± SD of three independent experiments. n = 5–8 animals per group. ∗P < 0.05 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.
Figure 4
Figure 4
Treatment with LLL reduces collagen deposition and alveolar enlargement in the lungs of COPD animals. The sections were stained with Sirius Red for collagen detection (a) and hematoxylin/eosin for alveolar enlargement (b). Data are expressed as mean ± SD. ∗P < 0.05 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.
Figure 5
Figure 5
Treatment with LLL reduces P2X7 receptor expression in the lungs of COPD animals. Lung samples were homogenized to determine the expression of the P2X7 receptor by the Western blotting technique. ∗P < 0.05 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.
Figure 6
Figure 6
Effect of treatment with LLL on static (a) and dynamic (b) elastance in the respiratory system. The animals were submitted to the anterior incision of the trachea, followed by cannulation of the same. Data are expressed as mean ± SD. n = 5–8 animals per group. ∗∗P < 0.01 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.
Figure 7
Figure 7
Effect of treatment with LLL on static (a) and dynamic (b) elastance in the lungs. The animals were submitted to the anterior incision of the trachea, followed by cannulation of the same. Data are expressed as mean ± SD. n = 5–8 animals per group. ∗P < 0.05 and ∗∗P < 0.01 in relation to the basal group; ϕP < 0.05 in relation to the COPD group.

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