Chronic exposure to diesel particles worsened emphysema and increased M2-like phenotype macrophages in a PPE-induced model

Moreira, Alyne Riani; Castro, Thamyres Barros Pereira de; Kohler, Júlia Benini; Ito, Juliana Tiyaki; Silva, Larissa Emidio de França; Lourenço, Juliana Dias; Almeida, Rafael Ribeiro; Santana, Fernanda; Brito, Jôse Mára de; Rivero, Dolores Helena Rodriguez Ferreira; Alonso-Vale, Maria Isabel Cardoso; Prado, Carla M.; Câmara, Niels Olsen Saraiva; Saldiva, Paulo Hilário Nascimento; Olivo, Clarice Rosa; Lopes, Fernanda Degobbi Tenório Quirino dos Santos

doi:10.1371/journal.pone.0228393

Cited by 17 publications

(6 citation statements)

References 55 publications

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“…Although polarization to M2 cannot be attributed to CETP alone, its presence exacerbated the effects of elastase. These findings suggest that the dominant accumulation of M2 in the presence of CETP in the lung should be explored in COPD ( 47 ). Interestingly, the accumulation of M2 macrophages was observed in adipose tissue and liver, in tissues with high expression of CETP and the lung, as well as in the blood of patients who suffered severe trauma, such as burns or sepsis.…”

Section: Discussionmentioning

confidence: 97%

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema

et al. 2021

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Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD.

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Section: Discussionmentioning

confidence: 97%

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema

et al. 2021

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“…Moreira et al. ( 50 ) used a model of emphysema that was induced by elastase and exposure to ultrafine particles of pollutants exhausted by diesel combustion. Their results showed an increase in the number of IL-10-positive cells compared to the control.…”

Section: Discussionmentioning

confidence: 99%

Modulating asthma–COPD overlap responses with IL-17 inhibition

Camargo,

Righetti,

de Almeida

et al. 2023

Front. Immunol.

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BackgroundIL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma–COPD overlap (ACO).MethodsIn this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers.ResultsAnti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1β, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-β, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05).ConclusionsOur results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3.

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“…Exposure protocol: The exposure was performed as previously described ( de Brito et al., 2018 ; Moreira et al., 2020 ). The animals were exposed through the stationary electric diesel exhaust generator (DE) (BD-2500 CFE; China).…”

Section: Methodsmentioning

confidence: 99%

Air Pollution’s Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy

Fonseca

Pessoa²,

Ribeiro³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundChagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis.MethodsWe studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-γ, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis.ResultsChagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups.ConclusionsA possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy.

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Chronic exposure to diesel particles worsened emphysema and increased M2-like phenotype macrophages in a PPE-induced model

Cited by 17 publications

References 55 publications

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema

Modulating asthma–COPD overlap responses with IL-17 inhibition

Air Pollution’s Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy

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