Role of NF-kappaB and PPAR-gamma in lung inflammation induced by monocyte-derived microparticles
Neri T, Armani C, Pegoli A, Cordazzo C, Carmazzi Y, Brunelleschi S, Bardelli C, Breschi MC, Paggiaro P, Celi A.
Eur Respir J
Cells used in publication:
Epithelial, airway, human
Tissue Origin: lung
Bronchial Epithelial Cell Growth Medium
Microparticles (MP) are phospholipid vesicles shed by cells upon activation or apoptosis. Monocyte-derived MP upregulate the synthesis of proinflammatory mediators by lung epithelial cells; the molecular bases of such activity are unknown. Peroxisome proliferatoractivated receptors (PPAR) have been demonstrated to be involved in the modulation of nuclear factor (NF)-kB transcriptional activity and inflammation. We investigated whether the upregulation of the synthesis of proinflammatory cytokines by human lung epithelial cells induced by monocyte/macrophage-derived MP involves NF-kB activation and is modulated by PPAR-c. MP were generated by stimulation of human monocytes/macrophages with the calcium ionophore, A23187. MP were incubated with human lung epithelial cells. NF-kB translocation was assessed by electrophoretic mobility shift assay. Interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 synthesis was assessed by ELISA and RT-PCR. Stimulation of A549 alveolar cells with monocyte/macrophage-derived MP caused an increase in NF-kB activation and IL-8 and MCP-1 synthesis that was inhibited by pre-incubation with the PPAR-c agonists, rosiglitazone and 15-deoxy-D12,14-prostaglandin-J2. Parallel experiments with normal human bronchial epithelial cells largely confirmed the results. The effects of PPAR-c agonists were reversed by the specific antagonist, GW9662. Upregulation of the synthesis of proinflammatory mediators by human lung epithelial cells induced by monocyte/macrophage-derived MP is mediated by NF-kB activation through a PPAR-c dependent pathway.
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