Interestingly it has been demon strated MDV3100 that reactive oxygen species can directly aug ment the activity of STAT6 raising the possibility Inhibitors,Modulators,Libraries that a decrease in reactive oxygen species Inhibitors,Modulators,Libraries as a result of NRF2 activation may inhibit STAT6 activity and inhibit Eotaxin 1 expression. Conclusions In summary, through gene expression profiling of normal human lung fibroblasts, following siRNA knockdown of NRF2 and KEAP1, we have identified Eotaxin 1 as a novel NRF2 regulated gene. Our data further define the role of this pathway in mediating inflammatory disease in the lungs. Airway remodeling in chronic asthma is characterized by epithelial detachment, subepithelial Cilengitide fibrosis, mucus hyperplasia, angiogenesis, airway edema, changes in the cartilage, and most obviously, an increase in airway smooth muscle mass.

It is believed that abnormalities in proliferation, apoptosis, migration, secretion, and con traction of smooth muscle cells all play roles in airway smooth Inhibitors,Modulators,Libraries muscle remodeling, and contribute to airway hyperresponsiveness. The cause for such abnormalities is complex and depends on a network of inflammatory mediators and cytokines. The levels of some mediators, such as PDGF and TGF b, are greatly elevated in the lung of asthmatic patient and are thought to play important roles in airway smooth muscle remodeling. In vitro studies have shown that PDGF is a potent SMC mitogen that can pro mote proliferation and migration while switching cells to an immature phenotype and, therefore, decreasing the contractility of the cells. However, the precise mechan isms underlying these processes remain unclear.

Reticulons are a family of proteins that include four family members, RTN 1, 2, 3, and 4. In mammals, the RTNs Inhibitors,Modulators,Libraries are mainly localized to the endoplasmic reticu lum and are involved in tubulogenesis of the ER and membrane curvature. Different isoforms of the RTN family have distinct functions. Recently, the RTN 4 iso forms, also called Nogo, have been demonstrated to be vital mediators of a variety of cellular responses and tis sue repair. The RTN 4 family is expressed in three splice variants including Nogo A, B, and C. Nogo A is pri marily expressed in the central nervous system and is identified as a potent inhibitor of axonal growth and repair. Nogo etc C exists mainly in skeletal muscle, whereas Nogo B is widely expressed in peripheral tissues including those of lung and vascular systems. Mice deficient in Nogo B exhibited an exaggerated neointimal proliferation that could be rescued by adenoviral mediated gene transfer of Nogo B.