interleukin-8 and andrographolide

Topics: Colorectal Neoplasms; Diterpenes; HCT116 Cells; Humans; Interleukin-8; Mitogen-Activated Protein Kinases; NADPH Oxidases; NF-kappa B; Reactive Oxygen Species; Signal Transduction; src-Family Kinases; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.

Topics: Alveolar Epithelial Cells; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Diterpenes; Drugs, Chinese Herbal; Gene Silencing; Glutathione; Humans; I-kappa B Proteins; Interleukin-6; Interleukin-8; MicroRNAs; NF-kappa B; NF-KappaB Inhibitor alpha; Nicotiana; Oxidative Stress; Smoke