MARIANGELA MACCHIONE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- Influence of particles from atmospheric pollution in female hormonal receptors in bronchi cells.>(2020) SMELAN, Juliana; ALMEIDA, Juliane; FRIAS, Daniela; BRENTANI, Mitzi; MACCHIONE, Mariangela
- Smoking load reduction is insufficient to downregulate miR-301b, a lung cancer promoter(2020) ARCAS, Camila dos Santos; LIN-WANG, Hui Tzu; UMEDA, Iracema Ioco Kikuchi; SOUSA, Marcio Goncalves de; UTIYAMA, Daniela Mitiyo Odagiri; MANSUR, Antonio de Padua; MACCHIONE, Mariangela; HIRATA, Mario Hiroyuki; NAKAGAWA, Naomi KondoSeveral circulating miRNAs identified in the plasma of smokers have been implicated as promoters of nasopharyngeal and lung carcinoma. To investigate the plasma profile of miRNAs in subjects who reduces the number of smoked cigarettes and who quit after six months. We accompanied 28 individuals enrolled in a Smoking Cessation Program over 6 months. At Baseline, clinical characteristics, co-morbidities, and smoking history were similar among subjects. After 6 months, two groups were defined: who successfully quitted smoking (named ""quitters"", n=18, mean age 57 years, 11 male) and who reduced the number of cigarettes smoked (20-90%) but failed to quit smoking (named ""smokers"", n=10, mean age 52 years, 3 male). No significant clinical changes were observed between groups at baseline and after a 6-month period, however, quitters showed significant downregulations in seven miRNAs at baseline: miR-17 (-2.90 -fold, p=0.029), miR-20a (-3.80-fold, p=0.021); miR-20b (-4.71-fold, p=0.027); miR-30a (-3.95-fold, p=0.024); miR-93 (-3.63-fold, p=0.022); miR-125a(-1.70 -fold, p= 0.038); and miR-195 (-5.37-fold, p=0.002), and after a 6-month period in 6 miRNAs: miR-17 (-5.30-fold, p=0.012), miR-20a (-2.04-fold, p=0.017), miR-20b (-5.44-fold, p=0.017), miR-93 (-4.00-fold, p=0.041), miR-101 (-4.82-fold, p=0.047) and miR-125b (-3.65-fold, p=0.025). Using time comparisons, only quitters had significant downregulation in miR-301b (-2.29-fold, p=0.038) after 6-month. Reductions in the number of smoked cigarettes was insufficient to change the plasma profile of miRNA after 6 months. Only quitting smoking (100% reduction) significantly downregulated miR-301b related to hypoxic conditions, promotion of cell proliferation, decreases in apoptosis, cancer development, and progression as increases in radiotherapy and chemotherapy resistance.
- Avaliação da qualidade de vida relacionada à saúde de cortadores de cana-de-açúcar nos períodos de entressafra e safra(2012) CARVALHO JUNIOR, Luiz Carlos Soares de; RAMOS, Ercy Mara Cipulo; TOLEDO, Alessandra Choqueta de; CECCATO, Aline Duarte Ferreira; MACCHIONE, Mariangela; BRAGA, Alfesio Luis Ferreira; RAMOS, DioneiOBJECTIVE: To assess health-related quality of life in sugarcane cutters. METHODS: Longitudinal study conducted in a sugar and ethanol plant located in the western region of the State of Sao Paulo (Southeastern Brazil) from April (pre-harvest) to October (harvest) 2010. A total of 44 sugarcane cutters, smokers and non-smokers, was evaluated in three periods: pre-harvest, at the end of the third month during harvest and at the end of harvest. Health-related quality of life was assessed by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Analysis of variance for repeated measures and the Friedman test were performed to compare quality of life among the periods. To identify the frequency of workers whose score increased in the harvest periods compared to pre-harvest (positive responders), the Goodman test was used, considering the qualitative variables of the SF-36 domains. RESULTS: At the end of pre-harvest, 23% workers drop out of work; 27% were smokers. There was a significant decrease in the vitality domain at the end of harvest compared to pre-harvest. The dropouts presented higher score in the social aspect domain compared to the group that remained working. There was no difference in health-related quality of life between smokers and non-smokers. However, there was a higher percentage of positive responders among non-smokers in the physical, social and emotional domains in the third month of harvest and in the general health status and social domains at the end of harvest, compared to smokers. CONCLUSIONS: Health-related quality of life in sugarcane cutters was reduced after the harvest period in the vitality domain. The individuals who remained working during harvest are those with lower scores for social aspects, which demonstrates the need to promote health assistance policies for this specific population, particularly during sugar harvest.
- Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil(2019) OLM, Mary Anne Kowal; MARSON, Fernando Augusto Lima; ATHANAZIO, Rodrigo Abensur; NAKAGAWA, Naomi Kondo; MACCHIONE, Mariangela; LOGES, Niki Tomas; OMRAN, Heymut; RACHED, Samia Zahi; BERTUZZO, Carmen Silvia; STELMACH, Rafael; SALDIVA, Paulo Hilario Nascimento; RIBEIRO, Jose Dirceu; JONES, Marcus Herbert; MAUAD, ThaisPrimary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis. Patients underwent at least two of the following tests: nasal nitric oxide, ciliary movement and analysis of ciliary immunofluorescence, and genetic tests (31 PCD genes + CFTR gene). The clinical characterization included the PICADAR and bronchiectasis scores, pulmonary function, chronic Pseudomonas aeruginosa (cPA) colonization, exhaled breath condensate (EBC) and mucus rheology (MR). Forty-nine of the 500 patients were diagnosed with definite (42/49), probable (5/49), and clinical (2/49) PCD. Twenty-four patients (24/47) presented bi-allelic pathogenic variants in a total of 31 screened PCD genes. A PICADAR score > 5 was found in 37/49 patients, consanguinity in 27/49, LD in 28/49, and eight PCD sibling groups. FACED diagnosed 23/49 patients with moderate or severe bronchiectasis; FEV1 <= 50% in 25/49 patients, eight patients had undergone lung transplantation, four had been lobectomized and cPA+ was determined in 20/49. The EBC and MR were altered in all patients. This adult PCD population was characterized by consanguinity, severe lung impairment, genetic variability, altered EBC and MR.
- Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice(2015) YOSHIZAKI, Kelly; BRITO, Jose Mara; MORIYA, Henrique T.; TOLEDO, Alessandra C.; FERZILAN, Sandra; OLIVEIRA, Ana Paula Ligeiro de; MACHADO, Isabel D.; FARSKY, Sandra H. P.; SILVA, Luiz F. F.; MARTINS, Milton A.; SALDIVA, Paulo H. N.; MAUAD, Thais; MACCHIONE, MariangelaBackground: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. Methods: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 mu g/m(3)). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 mu g/10 mu L of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-gamma) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). Results: DEP decreased IFN-gamma levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p <= 0.001) and CD8+ T cells (p <= 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p <= 0.001), and the index D2 was statistically different (p = 0.038) from the control animals. Conclusion: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.
- Nrf2 positively regulates autophagy antioxidant response in human bronchial epithelial cells exposed to diesel exhaust particles(2020) FRIAS, Daniela Perroni; GOMES, Raquel Labiapari Nunes; YOSHIZAKI, Kelly; CARVALHO-OLIVEIRA, Regiani; MATSUDA, Monique; JUNQUEIRA, Mara de Souza; TEODORO, Walcy Rosolia; VASCONCELLOS, Perola de Castro; PEREIRA, Daniela Cristina de Almeida; CONCEICAO, Paulo Roberto da; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; MACCHIONE, MariangelaDiesel exhaust particles (DEP) are known to generate reactive oxygen species in the respiratory system, triggering cells to activate antioxidant defence mechanisms, such as Keap1-Nrf2 signalling and autophagy. The aim of this study was to investigate the relationship between the Keap1-Nrf2 signalling and autophagy pathways after DEP exposure. BEAS-2B cells were transfected with silencing RNA (siRNA) specific to Nrf2 and exposed to DEP. The relative levels of mRNA for Nrf2, NQO1, HO-1, LC3B, p62 and Atg5 were determined using RT-PCR, while the levels of LCB3, Nrf2, and p62 protein were determined using Western blotting. The autophagy inhibitor bafilomycin caused a significant decrease in the production of Nrf2, HO-1 and NQO1 compared to DEPs treatment, whereas the Nrf2 activator sulforaphane increased the LC3B (p = 0.020) levels. BEAS-2B cells exposed to DEP at a concentration of 50 mu g/mL for 2 h showed a significant increase in the expression of LC3B (p = 0.001), p62 (p = 0.008), Nrf2 (p = 0.003), HO-1 (p = 0.001) and NQO1 (p = 0.015) genes compared to control. In siRNA-transfected cells, the LC3B (p < 0.001), p62 (p = 0.001) and Atg5 (p = 0.024) mRNA levels and the p62 and LC3II protein levels were decreased, indicating that Nrf2 modulated the expression of autophagy markers (R < 1). These results imply that, in bronchial cells exposed to DEP, the Nrf2 system positively regulates autophagy to maintain cellular homeostasis.
- Th17/Treg imbalance in COPD progression: A temporal analysis using a CS-induced model(2019) ITO, Juliana Tiyaki; CERVILHA, Daniela Aparecida de Brito; LOURENCO, Juliana Dias; GONCALVES, Natalia Gomes; VOLPINI, Rildo Aparecido; CALDINI, Elia Garcia; LANDMAN, Gilles; LIN, Chin Jia; VELOSA, Ana Paula Pereira; TEODORO, Walcy Paganelli Rosolia; TIBERIO, Iolanda de Fatima Lopes Calvo; MAUAD, Thais; MARTINS, Milton de Arruda; MACCHIONE, Mariangela; LOPES, Fernanda Degobbi Tenorio Quirino dos SantosBackground The imbalance between pro- and anti-inflammatory immune responses plays a pivotal role in chronic obstructive pulmonary disease (COPD) development and progression. To clarify the pathophysiological mechanisms of this disease, we performed a temporal analysis of immune response-mediated inflammatory progression in a cigarette smoke (CS)-induced mouse model with a focus on the balance between Th17 and Treg responses. Methods C57BL/6 mice were exposed to CS for 1, 3 or 6 months to induce COPD, and the control groups were maintained under filtered air conditions for the same time intervals. We then performed functional (respiratory mechanics) and structural (alveolar enlargement) analyses. We also quantified the NF-kappa B, TNF-alpha, CD4, CD8, CD20, IL-17, IL-6, FOXP3, IL-10, or TGF-beta positive cells in peribronchovascular areas and assessed FOXP3 and IL-10 expression through double-label immunofluorescence. Additionally, we evaluated the gene expression of NF-kappa B and TNF in bronchiolar epithelial cells. Results Our CS-induced COPD model exhibited an increased proinflammatory immune response (increased expression of the NF-kappa B, TNF-alpha, CD4, CD8, CD20, IL-17, and IL-6 markers) with a concomitantly decreased anti-inflammatory immune response (FOXP3, IL-10, and TGF-beta markers) compared with the control mice. These changes in the immune responses were associated with increased alveolar enlargement and impaired lung function starting on the first month and third month of CS exposure, respectively, compared with the control mice. Conclusion Our results showed that the microenvironmental stimuli produced by the release of cyto-kines during COPD progression lead to a Th17/Treg imbalance.
- Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice(2019) SANTANA, Fernanda P. R.; SILVA, Rafael C. da; GRECCO, Simone dos S.; PINHEIRO, Aruana J. M. C. R.; CAPERUTO, Luciana C.; ARANTES-COSTA, Fernanda M.; CLAUDIO, Samuel R.; YOSHIZAKI, Kelly; MACCHIONE, Mariangela; RIBEIRO, Daniel A.; TIBERIO, Iolanda F. L. C.; LIMA-NETO, Lidio G.; LAGO, Joao H. G.; PRADO, Carla M.Asthma allergic disease is caused by airway chronic inflammation. Some intracellular signaling pathways, such as MAPK and STAT3-SOCS3, are involved in the control of airway inflammation in asthma. The flavonoid sakuranetin demonstrated an anti-inflammatory effect in different asthma models. Our aim was to clarify how sakuranetin treatment affects MAPK and STAT3-SOCS3 pathways in a murine experimental asthma model. Mice were submitted to an asthma ovalbumin-induction protocol and were treated with vehicle, sakuranetin, or dexamethasone. We assayed the inflammatory profile, mucus production, and serum antibody, STAT3-SOCS3, and MAPK levels in the lungs. Morphological alterations were also evaluated in the liver. LPS-stimulated RAW 264.7 cells were used to evaluate the effects of sakuranetin on nitric oxide (NO) and cytokine production. In vivo, sakuranetin treatment reduced serum IgE levels, lung inflammation (eosinophils, neutrophils, and Th2/Th17 cytokines), and respiratory epithelial mucus production in ovalbumin-sensitized animals. Considering possible mechanisms, sakuranetin inhibits the activation of ERK1/2, JNK, p38, and STAT3 in the lungs. No alterations were found in the liver for treated animals. Sakuranetin did not modify in vitro cell viability in RAW 264.7 and reduced NO release and gene expression of IL-1 beta and IL-6 induced by LPS in these cells. In conclusion, our data showed that the inhibitory effects of sakuranetin on eosinophilic lung inflammation can be due to the inhibition of Th2 and Th17 cytokines and the inhibition of MAPK and STAT3 pathways, reinforcing the idea that sakuranetin can be considered a relevant candidate for the treatment of inflammatory allergic airway disease.
- Chemical composition modulates the adverse effects of particles on the mucociliary epithelium(2015) CARVALHO-OLIVEIRA, Regiani; PIRES-NETO, Ruy Camargo; BUSTILLOS, Jose Oscar Viega; MACCHIONE, Mariangela; DOLHNIKOFF, Marisa; SALDIVA, Paulo H. Nascimento; GARCIA, Maria Lucia BuenoOBJECTIVE: We compared the adverse effects of two types of real ambient particles; i.e., total suspended particles from an electrostatic precipitator of a steel mill and fine air particles from an urban ambient particulate matter of 2.5 mu m, on mucociliary clearance. METHOD: Mucociliary function was quantified by mucociliary transport, ciliary beating frequency and the amount of acid and neutral mucous in epithelial cells through morphometry of frog palate preparations. The palates were immersed in one of the following solutions: total suspended particles (0.1 mg/mL), particulate matter 2.5 mm 0.1 mg/mL (PM0.1) or 3.0 mg/mL (PM3.0) and amphibian Ringer's solution (control). Particle chemical compositions were determined by X-ray fluorescence and gas chromatography/mass spectrometry. RESULTS: Exposure to total suspended particles and PM3.0 decreased mucociliary transport. Ciliary beating frequency was diminished by total suspended particles at all times during exposure, while particulate matter of 2.5 mm did not elicit changes. Particulate matter of 2.5 mm reduced epithelial mucous and epithelium thickness, while total suspended particles behaved similarly to the control group. Total suspended particles exhibited a predominance of Fe and no organic compounds, while the particulate matter 2.5 mm contained predominant amounts of S, Fe, Si and, to a lesser extent, Cu, Ni, V, Zn and organic compounds. CONCLUSION: Our results showed that different compositions of particles induced different airway epithelial responses, emphasizing that knowledge of their individual characteristics may help to establish policies aimed at controlling air pollution.
- pH in exhaled breath condensate and nasal lavage as a biomarker of air pollution-related inflammation in street traffic-controllers and office-workers(2013) LIMA, Thamires Marques de; KAZAMA, Cristiane Mayumi; KOCZULLA, Andreas Rembert; HIEMSTRA, Pieter S.; MACCHIONE, Mariangela; FERNANDES, Ana Luisa Godoy; SANTOS, Ubiratan de Paula; BUENO-GARCIA, Maria Lucia; ZANETTA, Dirce Maria; ANDRE, Carmen Diva Saldiva de; SALDIVA, Paulo Hilario Nascimento; NAKAGAWA, Naomi KondoOBJECTIVE: To utilize low-cost and simple methods to assess airway and lung inflammation biomarkers related to air pollution. METHODS: A total of 87 male, non-smoking, healthy subjects working as street traffic-controllers or office-workers were examined to determine carbon monoxide in exhaled breath and to measure the pH in nasal lavage fluid and exhaled breath condensate. Air pollution exposure was measured by particulate matter concentration, and data were obtained from fixed monitoring stations (8-h work intervals per day, during the 5 consecutive days prior to the study). RESULTS: Exhaled carbon monoxide was two-fold greater in traffic-controllers than in office-workers. The mean pH values were 8.12 in exhaled breath condensate and 7.99 in nasal lavage fluid in office-workers; these values were lower in traffic-controllers (7.80 and 7.30, respectively). Both groups presented similar cytokines concentrations in both substrates, however, IL-1 beta and IL-8 were elevated in nasal lavage fluid compared with exhaled breath condensate. The particulate matter concentration was greater at the workplace of traffic-controllers compared with that of office-workers. CONCLUSION: The pH values of nasal lavage fluid and exhaled breath condensate are important, robust, easy to measure and reproducible biomarkers that can be used to monitor occupational exposure to air pollution. Additionally, traffic-controllers are at an increased risk of airway and lung inflammation during their occupational activities compared with office-workers.