ReviewRegulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies
Introduction
Epidemiological studies have associated exposure to ambient particulate matter (PM) with adverse cardiorespiratory effects (Dockery et al., 1993, Pope and Dockery, 1998, Pope et al., 1995, Schwartz et al., 1996). Proposed mechanisms behind PM-induced health effects are oxidant stress (Nel et al., 2001, Tao et al., 2003) and inflammation-associated injury (Dick et al., 2003, Ghio and Devlin, 2001). Recent in vitro studies with airway epithelial cells have demonstrated that exposure to pollution particles induces IL-8 production and various responses associated with oxidant stress, (Hetland et al., 2004, Li et al., 2002). Lung macrophages respond to PM by releasing a variety of cytokines, while showing decreased phagocytic function (Becker et al., 2003, Soukup and Becker, 2001).
Previous studies (Becker et al., 2002) have shown that ambient air pollution particles contain components which stimulate Toll like receptors 2 and 4 (TLR2 and TLR4). It was therefore proposed that components of whole Gram positive and Gram negative bacteria were associated with the particles, including the ubiquitously present lipopolysaccharide (LPS). In AM, the cytokine response to particles was inhibited by antibody to CD14 and an antagonist of TLR4, emphasizing the role of bacterial products in the response (Becker et al., 2002, Soukup and Becker, 2001). Also, airway epithelial cells have been shown to respond to various bacterial pathogens by the release of cytokines (Becker et al., 2004, Larsson et al., 1999). These cells have been shown to express several members of the TLR family of receptors (Becker et al., 2000), which are known to be involved in the recognition components of Gram-positive and -negative bacteria, viruses as well as fungal elements (Janssens and Beyaert, 2003). Therefore, epithelial cells may also respond to microbial products, other than LPS, contained in ambient air PM.
Diesel particles, which constitute the main mass of fine PM in some locations, induce negligible amounts of cytokine in AM compared to amounts induced following stimulation with ambient PM (Becker et al., 1996). Instead, the suppressive effect of diesel on cytokine production by LPS or other microbial products have been emphasized as a possible mechanism whereby diesel exerts its health effects (Amakawa et al., 2003, Yang et al., 2001). Fine pollution particles may have a similar effect to diesel since the major component of this size fraction in the area of collection (Chapel Hill, NC) is diesel dust. Experiments were conducted to compare suppressive effect of diesel, ambient fine and coarse PM, on LPS-induced cytokine production. Both PM size fractions were found to be strongly suppressive, and the effect of at least coarse PM unlikely to be related to organic compounds of diesel. Since cytokine induction by coarse PM, and fine PM, involved stimulation of TLR4, it is possible that these particles induce as state similar to well-documented LPS tolerance (Dobrovolskaia and Vogel, 2002, Nomura et al., 2000, Schwartz, 2002).
Section snippets
Particle collection
Ambient air particles: Particles were collected in Chapel Hill, North Carolina, using a ChemVol high Volume Cascade Impactor (Rupprecht and Patashnick Co. Albany, NY). Coarse PM and fine PM particles were collected for 72 h onto polyurethane foam (McMaster-Carr, Atlanta, GA), which were previously cleaned with methanol and water and dried under sterile conditions. Ultrafine particles were collected onto G5300 filters (Monandock Non-Wovens LLC, Mt. Pocono, PA).The foams/filters cut into strips
Oxidant stress
Although epidemiological studies have suggested that fine particles may be more detrimental to human health than coarse mode particles (Sarnat et al., 2001, Schwartz et al., 1996), in vitro studies (Becker et al., 2003, Hetland et al., 2004), and animal in vivo data (Dick et al., 2003, Dybing et al., 2004, Schins et al., 2004, Tao et al., 2003) have provided equivocal support for the preferential toxicity of fine particles. It was shown that coarse particles in AM and airway epithelial cells
Conclusion
Taken together, the selected experiments shown here demonstrate possible mechanisms whereby pollution particles affect lung health. If inflammation is involved as in asthma and inflammatory lung diseases, particles may exacerbate symptoms or obstruct a normal response. Proinflammatory measures appear to be the dominant response to coarse PM, which affect cytokine production and prostaglandin synthesis. This response appears to be driven by TLR2 and TLR4 stimulating compounds in both NHBE and
References (39)
- et al.
Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production
Toxicol. Appl. Pharmacol.
(1996) - et al.
CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium
J. Biol. Chem.
(2000) - et al.
TLR-2 is involved in airway epithelial cell response to air pollution particles
Toxicol. Appl. Pharmacol.
(2005) - et al.
Toll receptors, CD14, and macrophage activation and deactivation by LPS
Microbes Infect.
(2002) - et al.
Respiratory allergy adjuvant and inflammatory effects of urban ambient particles
Toxicology
(2004) - et al.
Release of inflammatory cytokines, cell toxicity and apoptosis in epithelial lung cells after exposure to ambient air particles of different size fractions
Toxicol. In Vitro
(2004) - et al.
Induction of prostaglandin H synthase 2 in human airway epithelial cells exposed to residual oil fly ash
Toxicol. Appl. Pharmacol.
(1996) - et al.
Inflammatory effects of coarse and fine particulate matter in relation to chemical and biological constituents
Toxicol. Appl. Pharmacol.
(2004) TLR4 and LPS hyporesponsiveness in humans
Int. J. Hyg. Environ. Health
(2002)- et al.
Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin
Toxicol. Appl. Pharmacol.
(2001)
Reactive oxygen species in pulmonary inflammation by ambient particulates
Free Radical Biol. Med.
Suppressive effects of diesel exhaust particles on cytokine release from human and murine alveolar macrophages
Exp. Lung Res.
Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages
J. Immunol.
Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles
Am. J. Respir. Cell Mol. Biol.
Response of human alveolar macrophages to ultrafine, fine, and coarse urban air pollution particles
Exp. Lung. Res.
Cytokine secretion by cystic fibrosis airway epithelial cells
Am. J. Respir. Crit. Care Med.
Message amplification phenotyping (MAPPing): a technique to simultaneously measure multiple mRNAs from small numbers of cells
BioTechniques
Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury
Am. J. Respir. Cell Mol. Biol.
Murine pulmonary inflammatory responses following instillation of size-fractionated ambient particulate matter
J. Toxicol. Environ. Health, A
Cited by (278)
Urban airborne PM<inf>2.5</inf> induces pulmonary fibrosis through triggering glycolysis and subsequent modification of histone lactylation in macrophages
2024, Ecotoxicology and Environmental SafetyShort-term exposure to ambient air pollution and hospital admissions for angina among older adults in South China
2024, Atmospheric EnvironmentInhalable Saharan dust induces oxidative stress, NLRP3 inflammasome activation, and inflammatory cytokine release
2023, Environment InternationalInflammation resolution in environmental pulmonary health and morbidity
2022, Toxicology and Applied PharmacologyShort-term and residential exposure to air pollution: Associations with inflammatory biomarker levels in adults living in northern France
2022, Science of the Total EnvironmentCitation Excerpt :Tsai et al. found a statistically significant association between short- and long-term exposure to PM10 and levels of three cytokines (IL1β, IL6, and TNFα); this is still the only study to have found an association with cytokine levels in the general population. It is plausible that air pollution increases inflammation and cytokine secretion, since in vitro studies have evidenced the production of TNFα by alveolar macrophages exposed to particulate air pollutants (van Eeden et al., 2001; Becker et al., 2005). Furthermore, exposure to air pollution can lead to an increase in oxidative stress (Imrich et al., 2007), a failure to eliminate apoptotic cells, and a state of chronic inflammation (Grabiec and Hussell, 2016; Robb et al., 2016).