Chronic Obstructive Pulmonary Disease-Derived Circulating Cells Release IL-18 and IL-33 under Ultrafine Particulate Matter Exposure in a Caspase-1/8-Independent Manner

Falco, Gianluigi De; Colarusso, Chiara; Terlizzi, Michela; Popolo, Ada; Pecoraro, Michela; Commodo, Mario; Minutolo, P.; Sirignano, Mariano; D’Anna, Andrea; Aquino, Rita Patrizia; Pinto, Aldo; Molino, Antonio; Sorrentino, Rosalinda

doi:10.3389/fimmu.2017.01415

Cited by 39 publications

(43 citation statements)

References 28 publications

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“…It has to be noted though, that as already published, the environmental pollution together smoking is another risk factor for lung cancer. Indeed, we found that smokers- and COPD-derived PBMCs treated with air pollutants [ 24 , 25 ], such as particulate matter (PM) of ultrafine sizes, were able to release caspase-4, index of higher risk for lung cancer establishment. A great limitation to this study is the absence of follow-up information about COPD and healthy smokers, in order to better understand and associate the levels of the circulating caspase-4 to the establishment of a tumor mass, avoiding late diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer

et al. 2018

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Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need.A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4. This test was validated by using i) plasma from 125 NSCLC patients and 79 healthy (non-pathological) subjects, ii) plasma from 139 smokers and iii) from 70 chronic-obstructive pulmonary disease (COPD) patients. Caspase-4 quantification was also assessed in the lung tumor mass of 98 paired NSCLC patients compared to 10 non-tumor lung tissues (i.e. tuberculosis).Circulating caspase-4 was detected in both healthy and NSCLC patients; however at different range values: 2.603–3.372 ng/ml for NSCLC patients (95% CI) compared to 0.3994-0.6219 ng/ml for healthy subjects (95% CI). The sensitivity of the test ranged from 97.07% to 100%; the specificity was 88.1% with a positive predictive value of 92.54%, accuracy of 95.19% and AUC of 0.971. Smokers (95% CI, 0.3947–0.6197 ng/ml) and COPD patients (95% CI, 1.703–2.995 ng/ml) showed intermediate values of circulating caspase-4. Tissue levels of caspase-4 in the tumor mass showed that 72 (72.7%) out of 99 patients were positive. More importantly, higher levels (cut-off value = 0.307 ng/ml) of caspase-4 in the tumor mass were associated to reduced overall survival (median 0.92 years) compared to NSCLC patients with lower levels (median 3.02 years).We report for the first time caspase-4 as a novel diagnostic and prognostic biomarker, opening new therapeutic perspectives for NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer

et al. 2018

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“…In our previous data (6, 7), we found that the release of IL-1-like cytokines from Soot-treated human cells was correlated to the inflammasome complex. Therefore, because caspase-1 is involved in the inflammasome activation and in IL-1-like cytokine release (12, 13), we treated mice with a well-known caspase-1 inhibitor, Ac-Y-Vad, Y-Vad.…”

Section: Resultsmentioning

confidence: 76%

“…Based on our previous published data, the administration of PMx can alter immune cell phenotype (6, 7). Therefore, we evaluated immune cell infiltration in the lung of the five groups of mice.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, it is nowadays well established that UFPs represent the most threatening particles in that they can localize into the low tract of the respiratory tree leading to pulmonary diseases (4). In this regard, we proved that UFPs, also defined as Soot, representative of those encountered in practical combustion conditions, including gasoline and diesel engines, induce pro-inflammatory pathways in smokers (6) and chornic pulmonary disease (COPD) patients (7).…”

Section: Introductionmentioning

confidence: 87%

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The Inhibition of Caspase-1- Does Not Revert Particulate Matter (PM)-Induced Lung Immunesuppression in Mice

et al. 2019

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Background: Air pollution is becoming a threatening issue for human health. Many epidemiological studies relate air pollution index to adverse effects in terms of disease incidence and/or disease exacerbation. In our previous studies, we found air pollutants can induce the release of pro-inflammatory cytokines from human peripheral blood cells. To better understand, the effects of air pollution in the lung, we took advantage of an animal model. Experimental Approach: Mice were intratracheally and daily exposed to urban collected particulate matter (PM, PM10, and PM1) and to the sub-micrometric carbonaceous component, Soot. Results: We found that PM10, PM1, and Soot promoted lung inflammation associated to higher bronchial responsiveness and lower dilation together with an immunosuppressive lung environment, characterized by tolerogenic dendritic cells (DCs), macrophages and myeloid -derived suppressor cells (MDSCs), the latter two Arginase I positive. In support, higher recruitment of Treg associated to higher levels of IL-10 were detected in the lung of PM10, PM1, and Soot treated mice. This effect was not abolished by the administration of a caspase-1 inhibitor, Ac-Y-VAD, implying that the canonical inflammasome complex was not associated to PMx-induced lung immunosuppression in mice. Conclusion: Our study proves that PM exposure leads to an immunosuppressive lung environment in a caspase-1-independent manner, paving the way to understand the molecular and cellular mechanism/s underlying the establishment of some respiratory disorders according to the exposure to air pollution.

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“…Indeed, another important characteristic of PEL+LAT combination is the antioxidant activity, which could be of potential relevance in oxidative stress-based pathologies, such as chronic obstructive pulmonary disease (COPD) [ 12 , 17 , 18 ]. In particular, we observed that PEL+LAT exerted a potentiated antioxidant activity on LPS-treated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and antimicrobial properties of Pelargonium sidoides DC and lactoferrin combination

Terlizzi

Colarusso

Maio³

et al. 2020

Bioscience Reports

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Lactoferrin (LAT), a multi-functional protein involved in numerous physiological functions, and the medicinal plant Pelargonium sidoides DC (PEL), have been described for their anti-inflammatory properties. Because the main advantage of natural products consists in administering them in combination rather than as single compound, we aimed to understand whether the combination of PEL and LAT, herein PELIRGOSTIM, could still prove beneficial or additive/synergistic activities during inflammatory conditions. To pursue this goal, we used macrophagic cells (J774.1) and treated them with PEL and LAT in a concentration-dependent manner. We found that PELIRGOSTIM was able to reduce the levels of reactive oxygen species (ROS) and nitrite, effects that were correlated to the release of lower levels of IL-1β after LPS treatment. In addition, the combination of PEL and LAT showed bacteriostatic activities against S. aureus and E. coli which had limited growth starting from 5 hours up to 20 hours. This effect was stronger than that observed for penicillin/streptomycin. Our results provide PELIRGOSTIM as an innovative combination of natural products capable to prevent inflammation-, oxidative stress- and microbial-related disorders.

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Chronic Obstructive Pulmonary Disease-Derived Circulating Cells Release IL-18 and IL-33 under Ultrafine Particulate Matter Exposure in a Caspase-1/8-Independent Manner

Cited by 39 publications

References 28 publications

Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer

Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer

The Inhibition of Caspase-1- Does Not Revert Particulate Matter (PM)-Induced Lung Immunesuppression in Mice

Antioxidant and antimicrobial properties of Pelargonium sidoides DC and lactoferrin combination

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