Background Gastric cancer (GC) is a common malignancy worldwide, with a major attribution to Helicobacter pylori. Interleukin (IL)-17A has been reported to be up-regulated in serum and tumor of GC patients, but the precise mechanisms underlying its involvement in gastric tumorigenesis are yet to be established. Here, we investigated the roles of IL-17A in the pathogenesis of H. pylori-induced GC. Methods GC was induced in IL-17A knockout (KO) and wild-type (WT) mice via N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. At 50 weeks after treatment, gastric tissues were examined by histopathology, immunohistochemistry, and immunoblot analyses. In vitro experiments on the human GC cell lines were additionally performed to elucidate the underlying mechanisms. Results Deletion of IL-17A suppressed MNU and H. pylori-induced gastric tumor development accompanied by a decrease in gastric epithelial cell growth, oxidative stress, and expression of gastric epithelial stem cells markers. In AGS cells, recombinant human IL-17A (rhIL-17A) inhibited apoptosis and G1/S phase transition arrest while promoting reactive oxygen species production, sphere formation ability of cancer stem cells (CSC), and expression of stemness-related genes. In addition, rhIL-17A induced expression of IL-17RC, leading to NF-κB activation and increased NADPH oxidase 1 (NOX1) levels. Inhibition of NOX1 with GKT136901 attenuated rhIL-17A-mediated elevation of GC cell growth, ROS generation, and CSC stemness. Clinically, IL-17RC expressions were significantly upregulated in human GC compared with normal gastric tissues. Conclusion Our results suggest that IL-17A promotes gastric carcinogenesis, in part, by regulating IL-17RC/NF-κB/NOX1 pathway, supporting its potential as a target in human GC therapy.

Chronic obstructive pulmonary disease (COPD) is a lung illness, marked by dyspnea, coughing, and sputum production. Cheonwangbosim-dan (CBD) is a traditional East Asian medicine, consisting of a combination of 15 medicinal herbs, which is frequently used to treat arterial/auricular flutter, neuroses, cardiac-malfunction-induced diseases, and insomnia. The present study evaluated the therapeutic effect of CBD (100 or 200 mg/kg) on COPD using a mouse model of COPD induced by cigarette smoke (CS) and lipopolysaccharide (LPS). The increase in inflammatory cell numbers caused by exposure to CS and LPS was significantly reduced by CBD administration. In addition, CBD therapy reduced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF). In lung tissue, CBD not only reduced the levels of IL-1β (CBD 100: p < 0.001 and CBD 200: p < 0.001), IL-6 (CBD 100: p < 0.001 and CBD 200: p < 0.001), TNF-α (CBD 100: p = 0.005 and CBD 200: p = 0.014), and monocyte chemoattractant protein-1 (MCP-1; CBD 100: p = 0.018 and CBD 200: p = 0.003), but also decreased the expression of α-smooth muscle actin (α-SMA; CBD 100: p < 0.001 and CBD 200: p < 0.001), transforming growth factor-β (TGF-β; CBD 100: p < 0.001 and CBD 200: p < 0.001), matrix metallopeptidase-7 (MMP-7; CBD 100: p = 0.019 and CBD 200: p < 0.001), MMP-9 (CBD 100: p = 0.015 and CBD 200: p = 0.013), and tissue inhibitor of metalloproteinase-1 (TIMP-1; CBD 100: p = 0.035 and CBD 200: p = 0.013) compared with the COPD group. CBD was also found to suppress the phosphorylation of nuclear factor kappa B (NF-κB), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinases (p38 MAPK). Taken together, these findings showed that CBD can attenuate respiratory inflammation and airway remodeling induced by exposure to CS and LPS, suggesting that CBD has probable preventive and therapeutic applications in patients with COPD.

Jakyakgamcho-tang (JGT) is used in oriental medicine to treat inflammation and allergy. Chronic obstructive pulmonary disease (COPD) causes respiratory inflammation, airway remodeling, and pulmonary emphysema. We examine the influence of JGT on COPD by using a mouse model. COPD was induced by inhalation of cigarette smoke (CS) and nasal administration of lipopolysaccharide (LPS). In comparison to COPD mice induced by CS and LPS, mice administered with JGT exhibited significantly lower amounts of inflammatory cells and reduced expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluid (BALF) and lung tissue. The elevated concentrations of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), and matrix metallopeptidase-9 (MMP-9) induced by CS and LPS were also inhibited by JGT treatment. Moreover, JGT suppressed CS and LPS-induced phosphorylation of nuclear factor kappa B (NF-κB), extracellular signal-regulated kinase1/2 (ERK1/2) and mitogen-activated protein kinases (p38 MAPKs). In a COPD mouse model, our results demonstrated that JGT prevented CS and LPS induced airway inflammation and remodeling.