Effect of Korean Red Ginseng and Rg3 on Asian Sand Dust-Induced MUC5AC, MUC5B, and MUC8 Expression in Bronchial Epithelial Cells

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases.

Respiratory and Systemic Toxicity of Inhaled Artificial Asian Sand Dust in Pigs

Air pollution, particularly caused by Asian sand dust (ASD) and particulate matter (PM), has become one of the leading threats to public health. However, the majority of studies have primarily focused on epidemiological assessment, and in vivo toxicities of certain air pollutants have been poorly elucidated in medium/large-size laboratory animals. To investigate the impact of ASD in domestic animals, 16 Landrace pigs were exposed to an artificial ASD sandstorm for 6 h. All animals were divided in four cages, and a commercial yellow soil was used for generating artificial mineralogical particles. Blood samples were collected, and necropsies were performed before exposure and 6, 12, 24, and 72 h after exposure. Complete blood cell count and the levels of serum biochemical enzymes, blood gas, electrolytes, and a variety of inflammatory cytokines were evaluated. In addition, histopathological examination was conducted. Various test results proved acute lower airway disorders with systemic inflammation in pigs. To our knowledge, this study is the first to describe experimental research in domestic animals concerning the damage caused by artificial ASD exposure. The results of this study suggest that ASD has importance in terms of not only public health but also of ultimate economic losses in the pork industry.

Asian Sand Dust Upregulates IL-6 and IL-8 via ROS, JNK, ERK, and CREB Signaling in Human Nasal Fibroblasts

Background Asian sand dust (ASD) profoundly affects respiratory health by inducing inflammation and causing upper airway inflammatory diseases. Interleukin (IL)-6 and IL-8 are pro-inflammatory mediators that are involved in upper airway inflammatory diseases. However, the effect of ASD on the production of IL-6 and IL-8 in nasal fibroblasts has not been adequately studied. We investigated the effect of ASD on the induction of pro-inflammatory mediators and its underlying mechanisms in nasal fibroblasts. Methods Real-time cytotoxicity assays were used to determine the effect of ASD on the viability of fibroblasts. Enzyme-linked immunosorbent assays and real-time polymerase chain reactions were performed to determine whether ASD induced the expression of IL-6 and IL-8. Reactive oxygen species (ROS) were quantified using 2, 7-dichlorofluorescein-diacetate and MitoSOX Red. Induction of IL-6 and IL-8 signal transduction pathways by ASD was confirmed by Western blotting. Ex vivo culture of the inferior turbinate tissue was performed to confirm the effects of ASD. Results ASD upregulated ROS levels, and this in turn promoted IL-6 and IL-8 expression through the MAPK (JNK and ERK) and CREB signaling pathways in nasal fibroblasts. However, ASD did not induce phosphorylation of p38. Specific inhibitors of each pathway (ROS, JNK, ERK, and CREB inhibitors) suppressed ASD-induced IL-6 and IL-8 upregulation. Conclusions ASD induces pro-inflammatory mediators, and the increased levels of IL-6 and IL-8 might be associated with the pathogenesis of chronic rhinosinusitis.

Asian Sand Dust Regulates IL-32 Production in Airway Epithelial Cells: Inhibitory Effect of Glucocorticoids

Purpose Epidemiologic studies have reported that Asian sand dust (ASD) is associated with chronic inflammatory diseases of the respiratory system. Glucocorticoids (GCs) have potent anti-inflammatory properties. The aims of this study were to evaluate the effects of GCs on ASD-induced interleukin-32 (IL-32) expression and to identify the underlying signaling pathways in airway epithelial cells. Methods A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxicity in A549 and human primary nasal epithelial cells. Expression levels of IL-32 messenger RNA and protein were measured by Western blot, real-time polymerase chain reaction, ELISA, and immunofluorescence staining. Signaling pathways were analyzed using specific inhibitors of Akt, MAPK, or NF- κB. The effects of GCs on the expression of ASD-induced IL-32 were confirmed with ex vivo organ cultures of the nasal interior turbinate. Results ASD (0–400 ng/mL) had no significant cytotoxic effects in A549 cells and human primary nasal epithelial cells. Expression levels of IL-32 were dose-dependently upregulated by ASD treatment in A549 cells. ASD induced phosphorylation of Akt, MAPK, and NF-κB, whereas GCs and specific inhibitors of Akt, MAPK, and NF-κB downregulated these activations and the expression of IL-32. These findings were further confirmed in human primary nasal epithelial cells and ex vivo organ cultures of the nasal interior turbinate. Conclusions GCs have an inhibitory effect on ASD-induced IL-32 expression via the Akt, MAPK, and NF- κB signaling pathways in airway epithelial cells.