NLRP3 inflammasome activation and lung fibrosis caused by airborne fine particulate matter

Zheng, Rong; Lan, Tao; Jian, Hui; Chang, Yun; Cheng, Yan; Yu, Feng; Zhang, Haiyuan

doi:10.1016/j.ecoenv.2018.07.076

Cited by 140 publications

(91 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A subsequent release enables adjacent epithelial cells to amplify this signal by stimulating the production of IL-1α, TNF-α, and IL-6. PM-induced activation of the inflammasome in the skin has not yet been studied; however in the pulmonary [247] and cardiovascular [248] systems, it was shown that PM activates the NLPR3 inflammasome in vivo (e.g., in mice).…”

Section: Pm-induced Activation Of Nf-κbmentioning

confidence: 99%

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Dijkhoff¹,

Drašler²,

Karakoçak³

et al. 2020

Part Fibre Toxicol

120

116

View full text Add to dashboard Cite

Background: Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles. Main text: To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health. Conclusion: Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.

show abstract

Section: Pm-induced Activation Of Nf-κbmentioning

confidence: 99%

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Dijkhoff¹,

Drašler²,

Karakoçak³

et al. 2020

Part Fibre Toxicol

120

116

View full text Add to dashboard Cite

show abstract

“…Aging was found to be associated with the increased production of mitochondrial reactive oxygen species, which led to NLRP3 inflammasome activation and IL-1β and IL-18 secretion [73,75]. The role of NLRP3 inflammasome has also been tested in other pulmonary fibrosis models including ventilator induced lung fibrosis, silica-induced fibrosis, and particular manner-induced fibrosis [68,74,76]. Although the NLRP3 inflammasome is mainly expressed in innate immune cells, there are several reports of inflammasome independent function of NLRP3 in murine fibrosis models.…”

Section: The Role Of Inflammasome-dependent Inflammation In Ipfmentioning

confidence: 99%

DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis

Cho

Lee

Stout‐Delgado

et al. 2020

IJMS

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease. Chronic lung inflammation is linked to the pathogenesis of IPF. DROSHA, a class 2 ribonuclease III enzyme, has an important role in the biogenesis of microRNA (miRNA). The function of miRNAs has been identified in the regulation of the target gene or protein related to inflammatory responses via degradation of mRNA or inhibition of translation. The absent-in-melanoma-2 (AIM2) inflammasome is critical for inflammatory responses against cytosolic double stranded DNA (dsDNA) from pathogen-associated molecular patterns (PAMPs) and self-DNA from danger-associated molecular patterns (DAMPs). The AIM2 inflammasome senses double strand DNA (dsDNA) and interacts with the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which recruits pro-caspase-1 and regulates the maturation and secretion of interleukin (IL)-1β and IL-18. A recent study showed that inflammasome activation contributes to lung inflammation and fibrogenesis during IPF. In the current review, we discuss recent advances in our understanding of the DROSHA–miRNA–AIM2 inflammasome axis in the pathogenesis of IPF.

show abstract

“…Cathepsin B release is known to activate NLRP3 inflammasome. [1] We showed that the use of a cathepsin B inhibitor significantly reduced the IL-1β production in THP-1 cells. TNF-α production follows the similar tread for different PMs.…”

Section: Discussionmentioning

confidence: 86%

“…We then evaluated the sub-chronic toxicity of PM2.5 in animal lung in vivo. [1] In terms of cytokine and growth factor presence in lungs, only the TGF-β1 production was statistically significant as well as the collagen deposition for sample S6. Eosinophil showed increase after PM exposures while lymphocyte and neutrophil cell counts were not significant in the total cell count suggesting the lack of lung inflammation.…”

Section: Discussionmentioning

confidence: 92%

“…It is the main source of haze and is a component of human induced air pollution. [1,2] While sources of particulates vary from natural origins like volcanoes to grassland fires, human activities such as burning fossil fuels in vehicles and power plants can also generate copious amounts of potentially harmful particulates, especially in urban areas. [3] Depending on the size of these particulates, they can gain access to different segment of the respiratory tracts and induce detrimental effects, which can lead to both pulmonary and cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Use of a Mechanism-based Toxicological Approach to Analyze the Pulmonary Pro-Fibrogenic Effects of Air Pollution PM2.5 Particulates

Cao¹,

Wang²,

Yan³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Airborne fine particulate matter (PM2.5) has been known capable of causing acute and chronic respiratory inflammation such as chronic obstructive pulmonary disease (COPD) and lung fibrosis. With incremental experience in the predictive toxicological approach on the potential adverse effects of nanomaterials, it is logical to explore the feasibility of using such a mechanism-based approach on PM2.5-induced lung toxicity. Results In this study, we collected a panel of eight PM2.5 samples for a comparative analysis of their pro-fibrogenic effects in the lung. These samples were collected on filters in November 2017 in Zhengzhou, Henan, China. In vitro screening shows although the PM2.5 particles did not induce significant cytotoxicity, they cause potent TNF-α and interleukin-1β (IL-1β) production in THP-1 cells as well as TGF-β1 in BEAS-2B lung epithelial cells. PM2.5 induced IL-1β production was shown to involve NLRP3 inflammasome activation, which was evidenced by the inhibited IL-1β production in NLRP3- and ASC-deficient cells and use of an inhibitor for cathepsin B, a known activation of the inflammasome through lysosomal damage pathway. Administration of PM2.5 to the lung in mice via oropharyngeal aspiration confirmed that the particles could induce TGF-β1 production in the bronchoalveolar lavage (BAL) fluid and collagen deposition in the lung at 21 days post-exposure, suggesting PM2.5 has the potential to induce pulmonary fibrosis. The ranking of the pro-fibrogenic effects by the PM2.5 samples in vivo was consistent with that of the IL-1β production in vitro. Conclusions In summary, we demonstrate that the PM2.5 is capable of inducing NLRP3 inflammasome activation and a series of cellular responses originating from the epithelial–mesenchymal trophic cell unit in the lung to induce fibrosis in vivo.

show abstract

NLRP3 inflammasome activation and lung fibrosis caused by airborne fine particulate matter

Cited by 140 publications

References 50 publications

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis

Use of a Mechanism-based Toxicological Approach to Analyze the Pulmonary Pro-Fibrogenic Effects of Air Pollution PM2.5 Particulates

Contact Info

Product

Resources

About