Nicole Cristine Rigonato Oliveira’s research while affiliated with Universidade Nove de Julho and other places

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/cm ² ) 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-1 β , 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.

Asthma is a chronic allergic airway inflammatory disease. Purinergic signaling, especially through the accumulation of extracellular adenosine triphosphate (ATP) activating P2X7 receptor (P2X7r) has a key role in asthma. Aerobic physical training (APT) improves allergic airway inflammation, but the role of purinergic signaling in its effects are unknown. Thus, 40 C57Bl/6 mice were distributed in Control, APT, HDM (dermatophagoides pteronyssinus), and HDM+APT groups. Treadmill APT was performed 5x/week, during 4 weeks after chronic allergic airway inflammation. APT in asthma groups reduced the accumulation of extracellular ATP in BAL (p<0.05) and the expression of CD73 and P2X7r by airway epithelium (p<0.001) and peribronchial leukocytes (p<0.001). HDM+APT also presented reduced the number of eosinophils (p<0.01) in BAL, as well as the levels of IL-4 (p<0.01), IL-5 (p<0.01) and IL-13 (p<0.01), while increased the IL-10 levels (p<0.01) in BAL. Airway collagen fibers deposition (p<0.01), elastic fibers deposition (p<0.01), smooth muscle thickness (p<0.01) and mucus production (p<0.01) was reduced in HDM+APT group. Airway hyperresponsiveness for methacholine 25 mg/mL (p<0.05) and 50 mg/mL (p<0.05) was also reduced in HDM+APT groups. In conclusion, aerobic physical training reduces asthma features by reducing CD73 leading to inhibition of ATP activating P2X7r.

Purpose: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-HT) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. Methods: Seventy-two C57Bl/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi) and Fibrosis+Exercise (Fi+Ex) groups. Bleomycin (1.5UI/Kg) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min a day, 5 days a week for 4 weeks. We evaluated total and differential cell counts in BAL, IL-1beta, IL-6, CXCL1/KC, IL-10, TNF-alpha and TGF-beta levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5HT2B receptor and Akt phosphorylation in lung tissue. Results: AT reduced bleomycin-increased number of total cells (p<0.001), neutrophils (p<0.01), macrophages (p<0.01) and lymphocytes (p<0.05) in BAL. AT also reduced the levels of IL-1beta (p<0.01), IL-6 (p<0.05), CXCL1/KC (p<0.001), TNF-alpha (p<0.001) and TGF-beta (p<0.001). AT increased expression of ant-inflammatory cytokine IL-10 (p<0.001). AT reduced bleomycin-increased 5-HT levels in BAL (p<0.001) and in serum (p<0.05). Reductions in collagen fiber deposition (p<0.01), 5-HT2B receptor expression (p<0.01) and Akt phosphorylation in lung tissue was observed. Conclusions: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling.

Low-level laser therapy (LLLT) is growing rapidly as an accredited anti-inflammatory therapy. However, its effects in models of inflammatory lung diseases are unknown. Therefore, this study investigated the effects of LLLT in two models of LPS-induced acute respiratory distress (ARDS). Intratracheal(i.t) LPS (10ug/mouse) and intraperitoneal (i.p) LPS (100ug/mouse) were used. LLLT consisted of (laser at 830nm, 3J/cm², 35mW, 80 seconds per point 3 points per application) in direct contact with the skin, beginning one hour after LPS administration, repeated consecutively for three times. BALB/c male mice were divided into control (n=6), LPS i.t (n=7), LPS i.p (n=7), LPS i.t. + LLLT (n=9), LPS i.p. + LLLT (n=9). Twenty-four hours after LPS administration, the animals were euthanized for evaluation of pulmonary inflammation by: Total and differential cell counts in bronchoalveolar lavage (BAL), analysis of cytokines levels in BAL and in serum (IL-1beta, IL-6, KC, and TNF-alpha) and through the quantitative analysis of the number of neutrophils in the lung parenchyma. The results showed that LLLT significantly reduced the levels LPS i.t. and LPS i.p. induce ARDS as demonstrated by reduced number of total cells (p<0.001) and neutrophils (p<0.001) in the BAL, reduced levels of IL-1beta, IL-6, KC, and TNF-alpha in BAL and in serum (p<0.001), beyond the number of neutrophils in the lung parenchyma (p<0.001). On the other hand, LLLT have not increased IL-10 levels. We conclude that low-level laser therapy at 830nm is effective in reducing pulmonary and systemic inflammation in models of LPS-induced ARDS independent of the etiology of the disease.