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Some pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant, a cell centrally involved in acute respiratory distress syndrome (ARDS); a syndrome lacking effective treatment. Considering the beneficial effects of the leukotriene receptor inhibitor, montelukast, on other lung diseases, whether montelukast attenuates inflammation in a mouse model of ARDS, and whether it reduces LPS stimulated activation of human neutrophils was investigated.Thirty-five C57Bl/6 mice were distributed into control (PBS)+24h, LPS+24h (10μg/mouse), control+48h, LPS+48h, and LPS 48h+Montelukast (10mg/kg). In addition, human neutrophils were incubated with LPS (1μg/mL) and treated with montelukast (10μM).Oral-tracheal administration of montelukast significantly attenuated total cells (P.05), macrophages (P.05), neutrophils (P.01), lymphocytes (P.001) and total protein levels in BAL (P.05), as well as IL-6 (P.05), CXCL1/KC (P.05), IL-17 (P.05) and TNF-α (P.05). Furthermore, montelukast reduced neutrophils (P.001), lymphocytes (P.01) and macrophages (P.01) in the lung parenchyma. In addition, montelukast restored BAL VEGF levels (P.05). LTB4 receptor expression (P.001) as well as NF-κB (P.001), a downstream target of LPS, were also reduced in lung parenchymal leukocytes. Furthermore, montelukast reduced IL-8 (P.001) production by LPS-treated human neutrophils.In conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils.

Creatine (Cr) is a substrate for adenosine triphosphate synthesis, and it is the most used dietary supplement among professional and recreative athletes and sportsmen. Creatine supplementation may increase allergic airway response, but the cellular and molecular mechanisms are unknown. We used murine model of OVA-induced chronic asthma and showed that Cr supplementation increased total proteins, ATP level, lymphocytes, macrophages, and IL-5 levels in BALF, as well as IL-5 in the supernatant of re-stimulated mediastinal lymph nodes. IL-5 and IL-13 expression by epithelial cells and by peribronchial leukocytes were increased by Cr. Cr augmented the expression of P2 × 7 receptor by peribronchial leukocytes and by epithelial cells, and increased the accumulation of eosinophils in peribronchial space and of collagen fibers in airway wall. In human cells, while Cr induced a release of ATP, IL-6, and IL-8 from BEAS-2B cells, whole blood cells, such as eosinophils, and CD4+ T cells, P2 × 7 receptor inhibitor (A740003) reduced such effects, as denoted by reduced levels of ATP, IL-6, and IL-8. Therefore, Cr supplementation worsened asthma pathology due to activation of airway epithelial cells and peribronchial leukocytes, involving purinergic signaling.

Pulmonary fibrosis is one of the most common interstitial diseases, which causes a great impact on the health of the affected population, has environmental and genetic risk factors, a poor prognosis and no effective treatment available. It is a normal consequence of tissue injury and chronic inflammation, characterized by accumulation and activation of excessive numbers of fibroblasts, deposition of extracellular matrix proteins (ECM), such as collagen, and distortion of normal tissue architecture. Photobiomodulation - PBM is a relatively new and effective therapy, low cost, with no side effects and possible use in the treatment of lung diseases. In this sense, the objective was to evaluate the inflammation and the level of TGF-b in the lung after PBM in an experimental model of fibrosis. We studied some parameters in C57BL/6 with fibrosis submitted to diode laser therapy (808nm, 30mW, 180s) for 15 days. The protocol used for the induction of fibrosis consisted of the application of bleomycin sulphate (1.5U/kg - orotracheal - 1x/day 0). Bronchoalveolar lavage (BAL) and lungs were collected for analysis. Data were submitted to the one-way ANOVA test followed by the Newman-Keuls test. Significance levels adjusted to 5% (p

The asthma is characterized by activation of Th2 lymphocytes and production of cytokines, eosinophilic inflammation, oedema and increased secretion of mucus. Thus, immunotherapeutic strategies, as photobiomodulation (PBM), aim at a negative regulation of cytokines, chemokines and transcription factors. Tregs lymphocytes are known to suppressing the migration of other effector cells (Th1, Th2 and Th17) and eosinophils into the tissues, as well as the release of inflammatory mediators. In this sense, the objective was to evaluate Foxp3 Treg cells, as well as the production of IL10 in the lung after PBM. We studied some parameters in Balb/C with Asthma submitted to diode laser therapy (660nm, 100mW, 150s) for 15 days. The protocol used for the induction of asthma consisted of sensitization with ovalbumin - OVA (day 0 and day 14) and orotracheal challenge on day 21 (3x per week/5 weeks). Bronchoalveolar lavage (BAL) and lungs were collected for analysis. The data were submitted to the One-way ANOVA test followed by the Newman-Keuls test. Significance levels adjusted to 5% (p

This study investigated the effects of aerobic exercise (AE) on both the maturation of dendritic cells (DC) and the activation of lymphocytes in a mouse model of chronic allergic airway inflammation.C57BL/6 mice distributed into control, exercise, ovalbumin (OVA), and OVA + exercise groups were submitted to OVA sensitization and challenge. Treadmill training was performed for 4 wk, and mice were assessed for classical features of chronic allergic airway inflammation as well as dendritic cell activation and T-lymphocyte response.AE reduced OVA-induced eosinophilic inflammation as observed in bronchoalveolar lavage fluid (P0.001), airway walls (P0001), and also reduced collagen deposition (P0.001). AE also reduced bronchoalveolar lavage fluid cytokines (interleukin [IL]-4, P0.001; IL-5, P0.01; IL-6, P0.001; IL-13, P0.01; and tumor necrosis factor α, P0.01). Cells derived from mediastinal lymphnodes of AE animals that were restimulated with OVA produced less IL-4 (P0.01), IL-5 (P0.01), and IL-13 (P0.001). In addition, AE reduced both DC activation, as demonstrated by reduced release of IL-6 (P0.001), CXCL1/KC (P0.01), IL-12p70 (P0.01), and tumor necrosis factor α (P0.05) and DC maturation, as demonstrated by lower MCH-II expression (P0.001).AE attenuated dendritic cell and lymphocyte activation and maturation, which contributed to reduced airway inflammation and remodeling in the OVA model of chronic allergic airway inflammation.

Creatine supplementation exacerbates asthma phenotype, but the cellular mechanisms involved in this response are unknown. Forty-Eight C57Bl/6 male mice (n = 2 x 6 mice/group) were distributed into Control (Co), Creatine (Cr), Ovalbumin (OVA) and Ovalbumin+Creatine (OVA+Cr) groups. A chronic model of ovalbumin (OVA)-induced asthma was used, when sensitization was done by using i.p. injections of OVA (400µg/mouse) on days 0, 14, 28 and 42 and aerosol challenge by using OVA solution (1%), 3x/week, from 21st-53rd day. Creatine supplementation (Cr; 0.5 g/kg/day) was administered from 21st-53rd day. Additionally, human cells, BEAS-2B, total leukocytes, eosinophils and CD4+ T lymphocytes were primed with IL-4 (1h prior Cr) and supplemented with Cr (10mM) for 4 hours. The in vivo study revealed that Cr increases total proteins, ATP levels, total cells, eosinophils and IL-5 and IL-13 levels in bronchoalveolar lavage (BAL), as well as IL-4, IL-5 and IL-13 levels in supernatant of re-stimulated mediastinal lymph nodes (MLN). Cr also increased the accumulation of collagen fibers on airway wall and mucus production. Immunohistochemistry (IHC) study revealed that Cr induced airway epithelial and peribronchial leukocytes activation. Under Cr stimuli, human (BEAS-2B, total leukocytes, eosinophils and CD4+ T cells) responded to increased release of ATP, TNF-alpha, IL-6 and IL-8. Creatine supplementation increases asthma phenotype through activation of airway epithelial cells and peribronchial leukocytes.

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were preincubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p0.01) and lung parenchyma (p0.01). AE reduced BAL inflammatory cytokines IL-1β, IL-6 and GM-CSF (p0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p0.01). Systemically, AE reduced IL-1β, IL-6 and IFN-gamma (p0.001), CXCL1/KC (p0.01) and TNF-alpha (p0.05). AE increased IL-10 levels in serum (p0.001) and BAL (p0.001). Furthermore, AE increased superoxide dismutase SOD (p0.01) and decreased superoxide anion accumulation in the lungs (p0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1β, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.

Fundacao de Amparo a Pesquisa de Sao Paulo (FAPESP), Sao Paulo, Brazil [12/51698-5] Background: Running economy (RE), expresses the relationship between the energy cost of running (Cr) and the work performed by a runner and is an predictor of performance. Given the intense effort of marathon runners during training and competition and the dearth of studies that address performance and cytokines in this population, the objective of the current study was to investigate the relationship between RE and cytokines in marathon runners. Methods: A total of 22 recreational marathon runners were examined. Using data obtained from VO2max assessments and sub-maximal tests, the following formula was applied to determine RE: Cr (mLO(2).kg(-1) . km(-1)) = VO2 (mL . kg(-1) . h(-1)) x 60 divided by speed (km . h(-1)). Results: Cr values shows no correlation with levels of the serum IL-1 beta, IL-4, IL-8, IL-10 and TNF-alpha 24h before, immediately after or 72h after the completion of an official marathon. However, the IL-6 level shows a significant correlation with Cr. Discussion and conclusion: The relationship between higher values of IL-6 and lower RE leads to the hypothesis of a physical under-recovery state by some athletes. Considering the stress caused by training, associated with the higher energetic cost in less economic athletes, it's possible that the period of resting may not totally compensate for the inflammatory state. Universidade Federal de São Paulo, Department of Otorhinolaryngology, Street of Otonis, 700, upper floor, Vila Clementino, CEP 04025-002, São Paulo - SP, Brazil Cruzeiro do Sul University, Institute of Sciences of Physical Activity and Sport (ICAFE), Galvão Bueno Street, 868, Liberdade, CEP 01506000, São Paulo - SP, Brazil [ Universidade Federal de São Paulo, Departament of Gynecology, Napoleão de Barros Street, 715, 7th floor, Vila Clementino, CEP 04024-002, São Paulo - SP, Brazil University Presbiterian Mackenzie, Departament of Developmental Disorders, Piauí Street, 181, Higienópolis, SP, Brazil Nove de Julho University, Departament of Biophotonic, Av. Dr. Adolpho Pinto, 109, Barra Funda, CEP 01156050, São Paulo-SP São Paulo, São Paulo, Brazil University of São Paulo, Departament of Sports, Av. Prof. Mello Moraes, 65, University city, CEP 05508-030, São Paulo - SP, Brazil Universidade Federal de São Paulo, Department of Otorhinolaryngology, Street of Otonis, 700, upper floor, Vila Clementino, CEP 04025-002, São Paulo - SP, Brazil Universidade Federal de São Paulo, Departament of Gynecology, Napoleão de Barros Street, 715, 7th floor, Vila Clementino, CEP 04024-002, São Paulo - SP, Brazil FAPESP: 12/51698-5 Web of Science

Air pollution is a growing problem worldwide, inducing and exacerbating several diseases. Among the several components of air pollutants, particulate matter (PM), especially thick (10–2.5 µm; PM 10) and thin (≤2.5 µm; PM 2.5), are breathable particles that easily can be deposited within the lungs, resulting in pulmonary and systemic inflammation. Although physical activity is strongly recommended, its effects when practiced in polluted environments are questionable. Therefore, the present study evaluated the pulmonary and systemic response of concomitant treadmill training with PM 2.5 and PM 10 exposure. Treadmill training inhibited PM 2.5- and PM 10-induced accumulation of total leukocytes (p

To evaluate whether periodontitis modulates lung inflammation in an experimental model of asthma as well as the photodynamic therapy (PDT) is associated with a reduction of lung inflammation. Seventy-two BALB/c male mice (~2 months) were randomly divided into 8 groups (n = 9): Basal, Periodontitis (P), P+PT, P+PT+PDT, Asthma (A), A+P, A+P+PT, and A+P+PT+PDT. Periodontitis was induced by using the ligature technique and asthma was induced by ovalbumin (OVA). PT was performed with curettes and PDT with methylene blue (0.005%), λ = 660nm, with a radiant exposure of 318J/cm2. After 43 days, euthanasia was carried out prior to lung and mandible morphological analyzes. All of the manipulations of the animals were performed by only one operator. The total and differential cell counts and cytokines IL-4, IL-5, IL-10, IFN-γ, TNF-α, IL-1β, and IL-6 were evaluated in the bronchoalveolar lavage (BAL) and in the serum. Mucus and alkaline phosphatase were also quantified. Statistical analyzes were performed by a blinded statistician. One-way analysis of variance (ANOVA) was employed, followed by the Student-Newman-Keuls test. Periodontitis group (P) increased alkaline phosphatase and bone resorption (p

Asthma is defined as a chronic lung disease of the airways associated with bronchial hyperresponsiveness with significant airflow limitation. Experimental models have been proposed to advance knowledge about the disease, as well as the discovery of new therapies. The Low Level Laser Therapy (LLLT) is a relatively new and effective, low cost, no side effects and possible use in the treatment of lung diseases. In this sense, aim of this study was evaluate the effect of LLLT 3J on chronic pulmonary inflammation in experimental model of asthma induced by HDM. BALB/c mice were divided four groups: control, HDM, LLLT 3J, HDM+LLLT 3J. Application of LLLT was 1 hour after the administration of HDM, with a wavelength of 660nm, power of 100m. Experimental model the animals were anesthetized with ketamine and xylazine and each animal received intra-tracheal administration of 100ug of HDM on days 0, 14, followed by three weekly administrations to day 42. On day 43, the animals were sacrificed and studied functional and structurally. Results indicate that LLLT reduced pulmonary inflammation by reducing the number of total cells in BAL (p

Introduction Leukotrienes (LTs) play a central role in asthma. Low- to moderate-intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma. Methods Sixty-four male, BALB/c mice were distributed into Control, Exercise (Exe), OVA, and OVA + Exe groups. Treadmill training was performed at moderate intensity, 5×/week, 1 h/session for 4 weeks. Quantification of bronchoalveolar lavage (BAL) cellularity, leukocytes, airway remodeling, interleukin (IL)-5, IL-13, cysteinyl leukotriene (CysLT), and leukotriene B4 (LTB4) in BAL was performed. In addition, quantitative analyses on peribronchial leukocytes and airway epithelium for LT pathway agents: 5-lypoxygenase (5-LO), LTA4 hydrolase (LTA4H), CysLT1 receptor, CysLT2 receptor, LTC4 synthase, and LTB4 receptor 2 (BLT2) were performed. Airway hyperresponsiveness (AHR) to methacholine (MCh) was assessed via whole body plethysmography. Results AE decreased eosinophils (p 0.001), lymphocytes (p 0.001) in airway walls. Collagen (p

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [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 (1.5 UI·kg) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min·d, 5 d·wk for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1β, IL-6, CXCL1/KC, IL-10, tumor necrosis factor α, and transforming growth factor β levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B 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. It also reduced the levels of IL-1β (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor α (P < 0.001), and transforming growth factor β (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It 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 were 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. &nbsp

A gravidade dos efeitos causados pela exposição ambiental e ocupacional ao benzeno determinou o controle de sua utilização. No entanto, mesmo nestas condições, toxicidade ao sistema imune e nervoso tem sido descrita. A toxicidade do benzeno é determinada pelos seus produtos de biotransformação, em que fenol (FE) e hidroquinona (HQ) têm papel relevante na imunotoxicidade. Neste contexto, o presente trabalho mostra que a exposição de ratos Wistar, machos, a doses de 5 ou 10 mg/kg de HQ (via i.p., uma vez ao dia, 13 doses consecutivas, com intervalos de 2 dias a cada 5 doses) provocou reduções acentuadas no influxo de leucócitos polimorfonucleares (PMN) e mononucleares (MN) para o pulmão 24 horas após inalação de Lipopolissacarídeo (LPS) de Salmonella abortus. Diferentemente, a migração de leucócitos em animais expostos ao FE não foi alterada. A exposição a ambos os agentes químicos simultaneamente (dose de 5 mg/kg cada) manteve a redução na migração de MN detectada em animais expostos à HQ e potencializou o efeito inibitório da HQ sobre a migração de leucócitos PMN. Os prejuízos nas migrações de leucócitos não foram decorrentes de modificações no número destas células na circulação. É importante ressaltar que os efeitos foram induzidos por doses dos agentes químicos que não causaram prejuízo à função hepática ou renal, determinados pela atividade das transaminases hepáticas e a concentração de creatinina no soro. Em conjunto, os dados obtidos mostram a exposição a baixas doses de HQ não provoca alterações nos parâmetros empregados como indicadores de toxicidade. No entanto, os efeitos tóxicos são manifestados resposta do organismo ao trauma.The high toxicity induced by occupational and environmental benzene exposure lead to its use restriction. However, at these conditions, neuronal and immune toxicity has been described. It is well known that benzene metabolites, such as hydroxyl compounds phenol (PHE) and hydroquinone (HQ), are responsible for immunotoxicity. In this context, it has shown herein that male Wistar rats exposed to HQ (doses of 5 or 10 mg/kg/day; 13 days with 2-day intervals every 5 doses) presented marked reduction in the number of mononuclear (MN) and polymorphonuclear (PMN) leukocytes in the bronchoalveolar fluid 24 hours after inhalation of Lipopolyssacaride of Salmonella abortus (LPS; 100 µg/mL). On the other hand, leukocyte migration into inflamed lungs was not altered in FE exposed rats, since values obtained were similar to those detected in control animals. Simultaneous exposure to HQ and PHE (5 mg/kg each compound) maintained the decreased number of MN cells observed in HQ exposed rats and potentiated the reduction of PMN cells induced by HQ exposure. The impaired leukocyte migration into inflamed lung did not reflect alterations on number of circulating cells. Moreover, it is important to emphasize that schedule of intoxication did not alter the functional ability of liver and kidney, as detected by normal activity of transaminases and creatinine concentration in the serum. Therefore, it is shown herein that in vivo exposures to lower doses of HQ do not alter end points used as biological indicators of toxicity, nevertheless toxic effects are evident after a host defense.

Idiopathic pulmonary fibrosis (IPF) is an interstitial disease with genetic and environmental risk factors. Experimental models attempt to clarify its pathophysiology and the discovery of new therapies. Therapy with low level laser therapy (LLL) is a possible use in the treatment of pulmonary diseases. Therefore this study investigated the effects of LLL on experimental model of bleomycin-induced IPF. C57BL/6 mice were divided into 3 groups: control, fibrosis and fibrosis+LLL. The animals received a single administration of bleomycin sulfate (1,5Ui/kg it). After 14 days animals started LLL (diodo laser, 660nm, 30mW e 3J / cm²) for 7 days (1x/day). 24 hours after the last irradiation, the animals were euthanized. Collected the bronchoalveolar lavage (BAL) and lungs. Three animals were used for the primary culture of pneumocytes type II and fibroblasts, stimulated with bleomycin with or without irradiated LLL. Evaluated the levels of IL1 β , IL6, TNFα, TGF β , IL10, IL17, IFNγ and KC in the supernatants of cells and BAL by ELISA. We also made collagen analysis airway, stained with Picrocirius. Immunohistochemistry was performed for quantification of PCNA and caspase 3. The results indicate that LLL reduced pulmonary inflammation, by reduction cell numbers in the BAL (p

Leukotrienes (LTs) play a central role in asthma. Moderate intensity aerobic exercise reduces asthmatic inflammation. Then, this study investigated if the anti-inflammatory effects of aerobic exercise is due to inhibition of LTs pathway.Forty male BALB/c mice were distributed in Control, Exercise, OVA and OVA+Exercise groups. Mice were sensitizedand challenged using ovalbumin. Moderate intensity treadmill training was performed 5x/week, 1h/session, for 4 weeks.Aerobic exercise decreased the number of eosinophils (p 0.001), lymphocytes (p 0.001) in airway wall. Also, airways collagen (p 1 receptor (p 2 receptor (p 2 receptor in lungs proteins extract. Finally, AHR was also reduced in OVA-trained mice at MCh 25mg/mL (p

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

Leukocytes play a central role in asthma physiopathology. Aerobic training (AT) reduces leukocytes recruitment to the airways, but the effects of AT on some aspects of leukocytes activation in asthma are unknown. Therefore, the effects of 4 weeks of AT on airway inflammation, pulmonary and systemic Th2 cytokines levels, leukocytes expression of pro and anti-inflammatory, pro-fibrotic, oxidants and anti-oxidants mediators in an experimental model of asthma was investigated. AT reduced the levels of IL-4, IL-5, IL-13 in bronchoalveolar lavage fluid (BALF) (p

Endocannabinoid signaling is terminated by enzymatic hydrolysis; process that 2-Arachidonoylglycerol (2-AG) is mediated by monoacylglycerol lipase (MAGL). The MAGL inhibition increases 2-AG levels, an endocannabinoid that acts on CB1 and CB2 receptors. In inflammation, the neutrophils are the first leukocytes to migrate to the injury focus. The aim was to investigate the effects of MAGL inhibition (with JZL184) in the neutrophils recruitment and activity in a murine model of acute lung injury (ALI) induced by LPS. Fifty C57BL/6 male mice were used (5–10/group) and divided into vehicle + saline, vehicle + LPS, and JZL184 + LPS groups. Mice were treated with JZL184 (16 mg/kg) or vehicle and after 60 min they received a LPS intranasal instillation (100 μg/ mL; 1 μL/g) or saline. Six, 24 and 48 h later mice were euthanized and bronchoalveolar lavage fluid and lungs were harvested to KC, MIP-2 and MPO analysis. The LPS was able to increase the KC, MIP-2 and MPO levels and the JZL184 treatment prevented all these parameters. The treatment with AM281 and AM230 (CB1 and CB2 antagonists, respectively), administered i.p. (2,5 and/or 5 mg/kg) 30 min before JZL184 treatment, showed that antagonists prevented the JZL184 anti-inflammatory effects. ALI establishment was evident 6, 24 and 48 h after LPS intranasal instillation and the MAGL inhibition has anti-inflammatory effects. CB1 and CB2 receptors were connected with JZL184 anti-inflammatory effects in ALI murine model. FAPESP2011/10181-7;2009/51886-3.