Casticin inhibits interleukin-1β-induced ICAM-1 and MUC5AC expression by blocking NF-κB, PI3K-Akt, and MAPK signaling in human lung epithelial cells

The compound casticin, isolated from Vitex rotundifolia, exerts anti-inflammatory effects and causes apoptosis of cancer cells. In this study, we explored the anti-inflammatory effects of casticin and modulation of cyclooxygenase (COX)-2, intercellular adhesion molecule 1 (ICAM-1), and mucin 5AC (MUC5AC) expression in interleukin-1 beta (IL-1 beta)-activated A549 human pulmonary epithelial cells. A549 cells were treated with various concentrations of casticin (5-20 mu M), and an inflammatory response was triggered with interleukin (IL)-1 beta cytokines. Casticin decreased levels of IL-6, tumor necrosis factor a, and IL-8 and suppressed COX-2 expression and prostaglandin E2 production. It also reduced MUC5AC, proinflammatory cytokine, and chemokine gene expression and inhibited ICAM-1 expression for monocyte adhesion in IL-1 beta-stimulated A549 cells. In addition, casticin inhibited phosphorylation of Akt, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) and blocked nuclear transcription factor kappa-B (NF-kappa B) subunit p65 protein translocation into the nucleus. Co-culture of NF-kappa B, MAPK, and PI3K inhibitors with casticin also led to more significantly suppressed ICAM-1 expression in inflammatory A549 cells. These results provide evidence that casticin has an anti-inflammatory effect by blocking proinflammatory cytokine, chemokine, and ICAM1 expression via suppression of the PI3K/Akt, NF-kappa B, and MAPK signaling pathways in IL-1 beta-stimulated inflammatory pulmonary epithelial cells.