Particulate matter with a diameter of 2.5 μm causes multiple pathological dysfunctions as presented by various biomarkers

Shawn Kaura; Yuchuan Ding

doi:10.4103/ed.ed_30_19

REVIEW ARTICLE

Year : 2019 | Volume : 4 | Issue : 3 | Page : 57-61

Particulate matter with a diameter of 2.5 μm causes multiple pathological dysfunctions as presented by various biomarkers

Shawn Kaura, Yuchuan Ding
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA

Date of Submission	03-Sep-2019
Date of Acceptance	06-Sep-2019
Date of Web Publication	27-Sep-2019

Correspondence Address:
Prof. Yuchuan Ding
Department of Neurosurgery, Wayne State University School of Medicine, 550 E Canfield, Room 48, Detroit, MI
USA

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ed.ed_30_19

Abstract

Particulate matter (PM) is a growing public health concern due to growing economy rooted in the worldwide technological development. PM with a diameter of 2.5 μm (PM_2.5) enters the body due to its small size and can accrue in the lungs, enter circulation, and deposit itself along the endothelial walls. Understanding the different types of PM and the various biomarkers that accumulate in the body is imperative to understanding mechanisms of disease development to create potential treatment plans. Three main effects of PM_2.5are examined: pro-inflammatory cytokines release upon exposure, DNA conformation breakage, and cancer metabolite accumulation. The pro-inflammatory cytokines release after periodical exposure to PM_2.5revealed that despite the concentration of PM, the bodily release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 was elevated. IL-8 was universally secreted in highest amounts by the body. The potential role that DNA conformation breakage could play in disease onset or progression in specifically hepatocyte cells showed that DNA conformation breakage was inevitable in disease progression. Cancer onset as a result of PM_2.5exposure was deemed attributable to reactive oxygen species properties in the PM as well as various metabolic dysfunctions. This mini-review examines some of the biomarkers that result from PM_2.5exposure and attempts to provide insight into how legislative and community efforts can curb the rising rates of PM in the air.

Keywords: Air pollution, hepatocyte DNA conformation breakage, oncometabolite accumulation, particulate matter, pro-inflammatory cytokines

How to cite this article:
Kaura S, Ding Y. Particulate matter with a diameter of 2.5 μm causes multiple pathological dysfunctions as presented by various biomarkers. Environ Dis 2019;4:57-61

How to cite this URL:
Kaura S, Ding Y. Particulate matter with a diameter of 2.5 μm causes multiple pathological dysfunctions as presented by various biomarkers. Environ Dis [serial online] 2019 [cited 2023 Jun 7];4:57-61. Available from: http://www.environmentmed.org/text.asp?2019/4/3/57/268152

Introduction

Particulate matter (PM) with a diameter of 2.5 μm, otherwise known as PM_2.5, is an umbrella term for ambient air pollution, which consists of hazardous waste products.^[1] These waste products house aerosolized components of both solids and liquids in the form of organic and inorganic molecules, dust, microorganisms, pollen, smoke, soot, etc.^[2] PM_2.5 is a direct byproduct of combusted elemental carbon as well as dust, and these two, along with other microcomponents of solids and liquids, can amalgamate until it forms PM_2.5.

PM_2.5 is a rising public health concern due to its cross-sector, worldwide impact in the fields of public health, human physiology, global burden, and economics. To fully understand the impacts in all of these sectors, it is important to note how grave the situation is. In 2010, 3.2 million deaths were attributable to PM_2.5.^[3] Since then, the World Health Organization estimates 7 million deaths per year due to PM_2.5 exposure. As the sixth-largest contributor to premature mortality, research into PM_2.5 is imperative. There have been multiple conclusions revealed about the relationship between high levels of PM_2.5 exposure and cardiovascular damage, hepatocyte malfunction, neuronal damage, various pulmonological disorders including asthma and chronic obstructive pulmonary disorder, and various embryological defects.^{[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]} There has been considerable evidence shed on the distinct effect PM_2.5 has on specific components of each of the aforementioned physiological organ systems. The biomarkers that result are the focus of this study.

PM_2.5 has aerodynamic properties given its 2.5 μm diameter.^[8] It can find multiple routes of entry into the human body, most commonly through the nasal and oral orifices.^[8] These entry routes make it quite feasible for the matter to accumulate in the lungs and enter circulation. Once the PM enters circulation, certain biomarkers become evident, and below are those most studied and the conclusions drawn. The biomarker study is one that attempts to understand the various physiological effects that PM_2.5 can have. Analyzing the different biomarkers that result of the exposure will grant clarity in understanding and diagnosing these various diseases as well as preventing the incidence of. The biomarkers studied consist of pro-inflammatory cytokines, hepatocyte DNA conformation breakage, oncometabolite accumulation, oxidative stress from reactive oxygen species (ROS), methylation, etc. In this mini-review, we discuss how these biomarkers indicate toxic effects in the body and the prevalence of certain biomarkers in comparison to others. Further, we discuss what certain biomarkers indicate in terms of disease onset and close with a brief overview of where future research is needed.

Particulate Matter With a Diameter Of 2.5 Micrometers and Pro-Inflammatory Cytokines

Pro-inflammatory cytokines are the human body's secretion of immune cells, such as helper T-cells as well as macrophages to promote inflammation. Promotion of inflammation is only instituted when the body is attempting to advance disease. This phenomenon is counter to cytokines inhibiting disease; such is the goal of anti-inflammatory cytokines. Examples of relevant pro-inflammatory cytokines whose impacts by PM exposure have been studied are interleukins (ILs) 6 and 8, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1. One study, to better understand the role that these pro-inflammatory cytokines take when exposed to PM_2.5, utilized a time-dependent study that measures the composition of PM_2.5 in the air (seasonal compositional difference between summer and winter) as well as the rate at which certain macrophages (pro-inflammatory cytokines) were secreted after a 3-h incubation period. It is noted that the summer and winter seasons have varying amounts of PM_2.5, with more PM_2.5 in the winter seasons. Both summer and winter seasons showed increases in the three aforementioned pro-inflammatory cytokines; however, the greatest and most statistically significant amounts were present during the winter months.^[16] The cytokine present in greatest amounts postexposure was TNF-α. To fully understand if this concept is universal is geographically dependent but does shed significant light on the cytokines mechanistically involved in PM exposure. Further studies exposed the relative amounts of cytokines released when exposed to PM_2.5, and the cytokine whose exposure was universally most significant and prevalent postexposure was IL-8.^[16] Further research would need to be done to understand why IL-8 is the most prevalent in cell damage induction.

Particulate Matter With a Diameter Of 2.5 Micrometers and Hepatocyte Dna Conformation Breakage

Any damage to such genes, through upregulation or downregulation, dysregulates our host equilibrium for battling illness, including exposure to PM_2.5.^[17] One study hypothesized that carbon black, a notorious postcombustive^[7] state of carbon emitted from diesel engines and fossil fuels, damages DNA conformation specifically in hepatocytes, which ultimately predisposes gene dysregulation^[18] and metabolic dysfunction^[19] as a result. To explore the DNA conformation change and ionic strength of carbon black, the researchers employed an ultraviolet-visible spectra study that uses fluorescence to analyze any changes in the DNA conformation.^[20] The study deduced that after 24 h of carbon black exposure, there was a significant break in DNA strands thereafter. This study aligns with other experiments that attempted to understand the role various PM_2.5 types have in DNA conformation. However, more studies indicate that ROS extrapolated from PM_2.5 contribute to the greatest amount of cell damage^[4] and DNA conformational change is inevitable in the process.^[20] One study attempted to understand how PM_2.5 affects epithelial cells, with consideration toward cancer, aging, and skin damage.^[21] After analysis, the study proved that ROS induced by PM_2.5 could stimulate apoptosis in skin cells. The study also showed that PM_2.5 causes DNA damage, mitochondrial dysfunction, intracellular molecular damage, reduced mitogen-activated protein kinase signaling,^[21] and lipid accumulation, leading to nonalcoholic fatty liver disease.^[9] In all literature reviewed, all of the aforementioned dysfunctions have shown consistent results stemming from PM_2.5 exposure. Further, to ensure universality of the effect on all DNA in different cells and with different exposures around the world, more research will be necessary.

Particulate Matter With a Diameter Of 2.5 Micrometers and Oncometabolite Accumulation

Oncometabolites are any metabolites that are associated with the promotion or development of cancer. The two biomarkers most evident throughout all literature reviewed are 2-hydroxyglutate and succinate.^[19] Both present in markedly increasing amounts in the cells are responsible for upregulation of autophagy, certain genes such as loc146880, and cause malignant behaviors in cancer.^[22] Of the literature reviewed, PM_2.5 is found to be highly correlated with the incidence of metabolic diseases.^[23] Furthermore, those with PM_2.5 exposure have a 15%–27% more likely chance of mortality. Certain cancer and morbid disease biomarkers are evident, especially in the most vital metabolic organs, such as liver.^[18],[23] The most prevalent biomarkers indicating rise in chronic inflammation, a precursor to cancer, are Toll-like receptor 4, nuclear factor kappa B, and c-Jun N-terminal kinase.^[19] One study examined the various metabolic dysfunctions associated with the oncometabolite accumulation using mice models. After 24-week exposure to PM_2.5, the mice exhibited oxidative stress and inflammation specifically, with the largest accumulation in the liver. While the mechanisms remain unclear, various cell organelles, such as the peroxisome, which are responsible for over 50 biochemical and metabolic pathways, showed dysregulation. Further, along with the liver, the bladder is susceptible to higher cancer rates depending on the concentration of PM_2.5 exposure.^[23] Two studies analyzed the rates of specifically bladder cancer and PM_2.5 exposure and deemed significant positive correlations between the aforementioned variables.^[10],[24] The biomarkers evident in such occurrences are as follows: increased amounts of exposure to polycyclic aromatic hydrocarbons result in an accumulation accruing in the body, NO₂, and SO₂.^[8],[25]

Perspective and Prospective

Reference [Figure 1] for a summary table of the aforementioned biomarkers. The biomarkers associated with PM_2.5 exposure after review are broader than originally thought. Considering the wide-ranging effect of PM_2.5, it is becoming evident that damage spans every cell in the body. The pathophysiology of the effects of PM_2.5 may be unclear; however, it does catalyze the release of pro-inflammatory cytokines (the biomarker of greatest significance was IL-8, regardless of the concentration of PM_2.5), causes DNA conformation changes and breaks, and accrues particulates that over periods cause various forms of cancer. While all of the physiological effects are not understood, it is evident that from the literature reviewed, any exposure of PM_2.5 will undoubtedly lead to forms of oxidative stress, inflammation, and multiorgan systemic cell destruction.^[10] Currently, the diagnosis for this amalgam of bodily stressors includes various forms of cancer, pulmonary disorders, cardiovascular diseases, nonalcoholic fatty liver disease,^[9] neuronal damage, and increased mortality rates worldwide.

Figure 1: A summation of the evident biomarkers when exposed to a common source of PM_2.5. The diagram showing the multiple pathways at play and some of the common resulting diseases. This figure is not comprehensive however does display the most common diseases connected to PM_2.5. Note that ROS and oncometabolite accumulation have a two-headed arrow. This arrowhead is indicative of a feedback effect, where the accumulation of ROS leads to an increase of oncometabolites and vice versa. *IL-8 was the most statistically significant pro-inflammatory cytokine upon exposure to PM_2.5 even when considering the season. PM_2.5: Particulate matter with a diameter of 2.5 μm, ROS: reactive oxygen species, IL: Interleukin

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Future Research Considerations

To move forward in not only understanding the physiological effects of PM_2.5, but also beginning to provide more apt screening and treatments, is only to be accomplished by more in-depth research. Of the literature reviewed, the mechanisms by which many of the statistically significant occurrences happened were not fully deduced. Therefore, from a pharmacological perspective, it will be difficult to find remedies for certain ailments due to the lack of understanding. Potential fields of study are the mechanisms involved in metabolism pathways after PM_2.5 exposures, oncometabolite development, and oxidative stress treatments. Despite the morbid nature of PM_2.5 exposure, potential treatments for the future include omega-3-rich fish oil antioxidants, legislative, and community efforts. To control the widespread air pollutants, it is important to understand humans' hand in its development. It is feasible to inhibit air pollutants by reducing number of car trips, carpooling, limiting electronic equipment usage, utilizing solar-powered electricity, etc.

Financial support and sponsorship

This work was partially supported by the Merit Review Award (I01RX-001964-01) from the US Department of Veterans Affairs Rehabilitation R&D Service.

Conflicts of interest

There are no conflicts of interest.

References

1.	Chen CC, Chen PS, Yang CY. Relationship between fine particulate air pollution exposure and human adult life expectancy in Taiwan. J Toxicol Environ Health A 2019;22:1-7.
2.	Anderson JO, Thundiyil JG, Stolbach A. Clearing the air: A review of the effects of particulate matter air pollution on human health. J Med Toxicol 2012;8:166-75.
3.	Apte JS, Marshall JD, Cohen AJ, Brauer M. Addressing global mortality from ambient PM2.5. Environ Sci Technol 2015;49:8057-66.
4.	Gosselin M, Zagury GJ. Metal(loid)s inhalation bioaccessibility and oxidative potential of particulate matter from chromated copper arsenate (CCA)-contaminated soils. Chemosphere 2019;238:124557.
5.	Peng J, Zhang L, Meng Q, Zhang F, Mao X, Liu J, et al. Adverse impact of ambient PM2.5 on expression and trafficking of surfactant protein A through reactive oxygen species damage to lamellar bodies. Toxicol Lett 2019;315:47-54.
6.	Saifipour A, Azhari A, Pourmoghaddas A, Hosseini SM, Jafari-Koshki T, Rahimi M, et al. Association between ambient air pollution and hospitalization caused by atrial fibrillation. ARYA Atheroscler 2019;15:106-12.
7.	Kelly FJ, Fussell JC. Linking ambient particulate matter pollution effects with oxidative biology and immune responses. Ann N Y Acad Sci 2015;1340:84-94.
8.	Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z, et al. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol 2010;299:C736-49.
9.	Xu MX, Ge CX, Qin YT, Gu TT, Lou DS, Li Q, et al. Prolonged PM2.5 exposure elevates risk of oxidative stress-driven nonalcoholic fatty liver disease by triggering increase of dyslipidemia. Free Radic Biol Med 2019;130:542-56.
10.	Kim HB, Shim JY, Park B, Lee YJ. Long-term exposure to air pollutants and cancer mortality: A meta-analysis of cohort studies. Int J Environ Res Public Health 2018;15. pii: E2608.
11.	Lu F, Xu D, Cheng Y, Dong S, Guo C, Jiang X, et al. Systematic review and meta-analysis of the adverse health effects of ambient PM2.5 and PM10 pollution in the Chinese population. Environ Res 2015;136:196-204.
12.	Kim W, Cho Y, Song MK, Lim JH, Kim JY, Gye MC, et al. Effect of particulate matter 2.5 on gene expression profile and cell signaling in JEG-3 human placenta cells. Environ Toxicol 2018;33:1123-34.
13.	Castañeda AR, Pinkerton KE, Bein KJ, Magaña-Méndez A, Yang HT, Ashwood P, et al. Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization. Toxicol Lett 2018;292:85-96.
14.	Duan J, Hu H, Zhang Y, Feng L, Shi Y, Miller MR, et al. Multi-organ toxicity induced by fine particulate matter PM2.5 in zebrafish (Danio rerio) model. Chemosphere 2017;180:24-32.
15.	Dadvand P, Nieuwenhuijsen MJ, Agustí À, de Batlle J, Benet M, Beelen R, et al. Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients. Eur Respir J 2014;44:603-13.
16.	Li R, Qiu X, Xu F, Lin Y, Fang Y, Zhu T, et al. Macrophage-mediated effects of airborne fine particulate matter (PM2.5) on hepatocyte insulin resistance in vitro. ACS Omega 2016;1:736-43.
17.	Popadić D, Heßelbach K, Richter-Brockmann S, Kim GJ, Flemming S, Schmidt-Heck W, et al. Gene expression profiling of human bronchial epithelial cells exposed to fine particulate matter (PM2.5) from biomass combustion. Toxicol Appl Pharmacol 2018;347:10-22.
18.	Ding D, Ye G, Lin Y, Lu Y, Zhang H, Zhang X, et al. MicroRNA-26a-CD36 signaling pathway: Pivotal role in lipid accumulation in hepatocytes induced by PM2.5 liposoluble extracts. Environ Pollut 2019;248:269-78.
19.	Ye G, Ding D, Gao H, Chi Y, Chen J, Wu Z, et al. Comprehensive metabolic responses of HepG2 cells to fine particulate matter exposure: Insights from an untargeted metabolomics. Sci Total Environ 2019;691:874-84.
20.	Zhang Q, Luo Q, Yuan X, Chai L, Li D, Liu J, et al. Atmospheric particulate matter2.5 promotes the migration and invasion of hepatocellular carcinoma cells. Oncol Lett 2017;13:3445-50.
21.	Zhen AX, Hyun YJ, Piao MJ, Fernando PD, Kang KA, Ahn MJ, et al. Eckol inhibits particulate matter 2.5-induced skin keratinocyte damage via MAPK signaling pathway. Mar Drugs 2019;17. pii: E444.
22.	Deng X, Feng N, Zheng M, Ye X, Lin H, Yu X, et al. PM2.5 exposure-induced autophagy is mediated by lncRNA loc146880 which also promotes the migration and invasion of lung cancer cells. Biochim Biophys Acta Gen Subj 2017;1861:112-25.
23.	Zhang R, Zhang X, Jia C, Pan J, Liu R. Carbon black induced DNA damage and conformational changes to mouse hepatocytes and DNA molecule: A combined study using comet assay and multi-spectra methods. Ecotoxicol Environ Saf 2019;170:732-8.
24.	Yeh HL, Hsu SW, Chang YC, Chan TC, Tsou HC, Chang YC, et al. Spatial analysis of ambient PM2.5 exposure and bladder cancer mortality in Taiwan. Int J Environ Res Public Health 2017;14. pii: E508.
25.	Wang C, Meng Z, Yao P, Zhang L, Wang Z, Lv Y, et al. Sources-specific carcinogenicity and mutagenicity of PM2.5-bound PAHs in Beijing, China: Variations of contributions under diverse anthropogenic activities. Ecotoxicol Environ Saf 2019;183:109552.