Airborne fine particulate matter with an aerodynamic diameter equal to or smaller than 2.5 μ m is abbreviated as PM 2.5 , which is one of the main components in air pollution. Exposure to PM 2.5 is associated with increased risk of many human diseases, including chronic and allergic rhinitis, but the underlying molecular mechanism for its toxicity has not been fully elucidated. We have hypothesized that PM 2.5 may cause oxidative stress and enhance inflammatory responses in nasal epithelial cells. Accordingly, we used human RPMI 2650 cells, derived from squamous cell carcinoma of the nasal septum, as a model of nasal epithelial cells, and exposed them to PM 2.5 that was collected at Fudan University (31.3°N, 121.5°E) in Shanghai, China. PM 2.5 exposure decreased the viability of RPMI 2650 cells, suggesting that PM 2.5 may impair the barrier function of nasal epithelial cells. Moreover, PM 2.5 increased the levels of intracellular reactive oxygen species (ROS) and the nuclear translocation of NF-E2-related factor-2 (Nrf2). Importantly, PM 2.5 also decreased the activities of superoxide dismutase, catalase and glutathione peroxidase. Pretreatment with N-Acetyl-L-cysteine (an anti-oxidant) reduced the degree of the PM 2.5 -induced oxidative stress in RPMI 2650 cells. In addition, PM 2.5 increased the production of granulocyte-macrophage colonystimulating factor, tumor necrosis factor-α, interleukin-13 and eotaxin (C-C motif chemokine ligand 11), each of which initiates and/or augments local inflammation. These results suggest that PM 2.5 may induce oxidative stress and inflammatory responses in human nasal epithelial cells, thereby leading to nasal inflammatory diseases. The present study provides insights into cellular injury induced by PM 2.5 .

Upper airway diseases including sinonasal disorders may be caused by exposure to fine particulate matter (≤2.5 μm; PM2.5), as proven by epidemiological studies. PM2.5 is a complex entity whose chemical constituents and physicochemical properties are not confined to a single, independent "particle" but which in this study means a distinctive environmental "toxin." The mechanism whereby PM2.5 induces nasal epithelial barrier dysfunction leading to sinonasal pathology remains unknown. In the present study, human nasal epithelial cells were exposed to non-cytotoxic doses of PM2.5 to examine how PM2.5 affects the nasal epithelial barrier. Tight junction (TJ) integrity and function were assessed by transepithelial electric resistance and paracellular permeability. The expression levels of TJ proteins such as zona occludens-1, occludin and claudin-1 were assessed by immunofluorescence staining and western blot. PM2.5 exposure induced epithelial barrier dysfunction as reflected by increased paracellular permeability and decreased transepithelial electric resistance. TJ proteins zona occludens-1, occludin and claudin-1 were found to be downregulated. Pretreatment with N-acetyl-l-cysteine alleviated PM2.5-mediated reactive oxygen species generation in RPMI 2650 cells, further preventing barrier dysfunction and attenuating the degradation of TJ proteins. These results suggest that PM2.5 induces nasal epithelial barrier disruption via oxidative stress, and N-acetyl-l-cysteine counteracts this PM2.5-mediated effect. Thus, nasal epithelial barrier disruption caused by PM2.5, which leads to sinonasal disease, may be prevented or treated through the inhibition of reactive oxygen species.

Exposure to PM2.5 (particulate matter ≤2.5 μm) increases the risk of nasal lesions, but the underlying mechanisms, especially the mechanisms leading to mitochondrial damage, are still unclear. Thus, we investigated the in vivo effects of PM2.5 exposure on the inflammatory response, oxidative stress, the enzyme activities of Na+K+-ATPase and Ca2+-ATPase, and the morphology and function of mitochondria in the nasal mucosa of rats. Exposure to PM2.5 occurred through inhalation of a PM2.5 solution aerosol. The results show that the PM2.5 exposure induced increased levels of malondialdehyde (MDA) and levels of proinflammatory mediators, including interleukin 6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). These changes were accompanied by decreases in the activities of total superoxide dismutase (T-SOD), Na+K+-ATPase, and Ca2+-ATPase in rat nasal mucosa. PM2.5 significantly affected the expression of specific mitochondrial fission/fusion genes (OPA1, Mfn1, Fis1, and Drp1) in nasal mucosa. These changes were accompanied by abnormal alterations of mitochondrial structures, including mitochondrial swelling, cristae disorder, and even fission resulting from higher doses of PM2.5. Our data shows that oxidative damage, inflammatory response, and mitochondrial dysfunction may be the toxic mechanisms that cause nasal lesions after exposure to PM2.5.