Particulate matter (PM) is the principal component of air pollution. PM includes a range of particle sizes, such as coarse, fine, and ultrafine particles. Particles that are <100 nm in diameter are defined as ultrafine particles (UFPs). UFPs are found to a large extent in urban air as both singlet and aggregated particles. UFPs are classified into two major categories based on their source. Typically, UFPs are incidentally generated in the environment, often as byproducts of fossil fuel combustion, condensation of semivolatile substances or industrial emissions, whereas nanoparticles are manufactured through controlled engineering processes. The primary exposure mechanism of PM is inhalation. Inhalation of PM exacerbates respiratory symptoms in patients with chronic airway diseases, but the mechanisms underlying this response remain unclear. This review offers insights into the mechanisms by which particles, including UFPs, influence airway inflammation and discusses several mechanisms that may explain the relationship between particulate air pollutants and human health, particularly respiratory health. Understanding the mechanisms of PM-mediated lung injury will enhance efforts to protect at-risk individuals from the harmful health effects of air pollutants.

Air pollutants include toxic particles and gases emitted in large quantities from many different combustible materials. They also include particulate matter (PM) and ozone, and biological contaminants, such as viruses and bacteria, which can penetrate the human airway and reach the bloodstream, triggering airway inflammation, dysfunction, and fibrosis. Pollutants that accumulate in the lungs exacerbate symptoms of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Asthma, a heterogeneous disease with complex pathological mechanisms, is characterized by particular symptoms such as shortness of breath, a tight chest, coughing, and wheezing. Patients with COPD often experience exacerbations and worsening of symptoms, which may result in hospitalization and disease progression. PM varies in terms of composition, and can include solid and liquid particles of various sizes. PM concentrations are higher in urban areas. Ozone is one of the most toxic photochemical air pollutants. In general, air pollution decreases quality of life and life expectancy. It exacerbates acute and chronic respiratory symptoms in patients with chronic airway diseases, and increases the morbidity and risk of hospitalization associated with respiratory diseases. However, the mechanisms underlying these effects remain unclear. Therefore, we reviewed the impact of air pollutants on airway diseases such as asthma and COPD, focusing on their underlying mechanisms.

Spermidine is an endogenous biological polyamine that plays various longevity-extending roles and exerts antioxidative, antiaging, and cell growth-promoting effects. We previously reported that spermidine levels were significantly reduced in idiopathic pulmonary fibrosis (IPF) of the lung. The present study assessed the potential beneficial effects of spermidine on lung fibrosis and investigated the possible mechanism. Lung fibrosis was established in mice using bleomycin (BLM), and exogenous spermidine was administered daily by intraperitoneal injection (50 mg/kg in phosphate-buffered saline). BLM-induced alveolar epithelial cells showed significant increases in apoptosis and endoplasmic reticulum stress (ERS)-related mediators, and spermidine attenuated BLM-induced apoptosis and activation of the ERS-related pathway. Senescence-associated β-gal staining and decreased expression of p16 and p21 showed that spermidine ameliorated BLM-induced premature cellular senescence. In addition, spermidine enhanced beclin-1-dependent autophagy and autophagy modulators in IPF fibroblasts and BLM-induced mouse lungs, in which inflammation and collagen deposition were significantly decreased. This beneficial effect was related to the antiapoptotic downregulation of the ERS pathway, antisenescence effects, and autophagy activation. Our findings suggest that spermidine could be a therapeutic agent for IPF treatment.

Idiopathic pulmonary fibrosis (IPF) is a progressive and destructive lung disease with a poor prognosis resulting in a high mortality rate. IL-37 is an anti-inflammatory cytokine that inhibits innate and adaptive immunity by downregulating proinflammatory mediators and pathways. However, the exact role of IL-37 in lung fibrosis is unclear. In this study, we found that the IL-37 protein was expressed in alveolar epithelial cells (AECs) and alveolar macrophages in healthy controls but significantly reduced in patients with IPF. IL-37 significantly inhibited oxidative stress–induced primary mouse AEC death in a dose-dependent manner, and knockdown of IL-37 significantly potentiated human lung cancer–derived AEC (A549 cells) death. IL-37 attenuated constitutive mRNA and protein expression of fibronectin and collagen I in primary human lung fibroblasts. IL-37 inhibited TGF-β1–induced lung fibroblast proliferation and downregulated the TGF-β1 signaling pathway. Moreover, IL-37 enhanced beclin-1–dependent autophagy and autophagy modulators in IPF fibroblasts. IL-37 significantly decreased inflammation and collagen deposition in bleomycin-exposed mouse lungs, which was reversed by treatment with the autophagy inhibitor 3-methyladenine. Our findings suggested that a decrease in IL-37 may be involved in the progression of IPF and that IL-37 inhibited TGF-β1 signaling and enhancement of autophagy in IPF fibroblasts. Given its antifibrotic activity, IL-37 could be a therapeutic target in fibrotic lung diseases, including IPF.

Kim BG, et al. Allergy Asthma Immunol Res. 2016 May;8(3):246-256. https://doi.org/10.4168/aair.2016.8.3.246

Kim BG, et al. Allergy Asthma Immunol Res. 2017 May;9(3):257-264. https://doi.org/10.4168/aair.2017.9.3.257