Combined Beta-agonists and corticosteroids do not inhibit extracellular matrix protein production in vitro.

Background. Persistent asthma is characterized by airway remodeling. Whereas we have previously shown that neither β(2)-agonists nor corticosteroids inhibit extracellular matrix (ECM) protein release from airway smooth muscle (ASM) cells, the effect of their combination is unknown and this forms the rationale for the present study.

Dual ERK and phosphatidylinositol 3-kinase pathways control airway smooth muscle proliferation: differences in asthma.

Hyperplasia of airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely due to increased muscle proliferation. We have shown that ASM cells obtained from asthmatic patients proliferate faster than those obtained from non-asthmatic patients. In ASM from non-asthmatics, mitogens act via dual signaling pathways (both ERK- and PI 3-kinase-dependent) to control growth.

A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro.

Background: Airway smooth muscle (ASM) cells may contribute to airway remodeling through the release of growth factors, cytokines, and extracellular matrix (ECM) proteins. The effect of current asthma therapies on this release is not known.

Objective: We examined the effect of corticosteroids, long-acting beta(2)-agonists, and a phosphodiesterase 4 (PDE4) inhibitor on ASM-released connective tissue growth factor (CTGF), collagen I, fibronectin, versican, and IL-6.

Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix.

Airway remodeling describes the structural changes that occur in the asthmatic airway that include airway smooth muscle hyperplasia, increases in vascularity due to angiogenesis, and thickening of the basement membrane. Our aim in this study was to examine the effect of transforming growth factor-beta on the release of connective tissue growth factor and vascular endothelial growth factor from human airway smooth muscle cells derived from asthmatic and nonasthmatic patients. In addition we studied the immunohistochemical localization of these cytokines in the extracellular matrix after stimulating bronchial rings with transforming growth factor-beta.

pDMAEMA is internalised by endocytosis but does not physically disrupt endosomes.

Earlier workers proposed that poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA) facilitates cell transfection by being endocytosed, complexed with DNA, and subsequently acting as a "proton sponge" to burst endosomes/lysosomes and release DNA to the cytosol. It also seemed feasible that the cytotoxicity of pDMAEMA might result from lysosomal bursting, which can induce cell death. Experiments were performed to determine the extent of cytotoxicity of uncomplexed pDMAEMA, the mode of cell death it induces (i.

Extracellular matrix proteins modulate asthmatic airway smooth muscle cell proliferation via an autocrine mechanism.

Background: Airway remodeling is a key feature of persistent asthma and includes alterations in the extracellular matrix protein profile around the airway smooth muscle (ASM) and hyperplasia of the ASM. We have previously shown that nonasthmatic ASM cells in culture produce a range of extracellular matrix protein proteins and that asthmatic ASM cells proliferate faster than cells from nonasthmatic patients.

Objective: In this study, we compared the profile of extracellular matrix proteins produced by nonasthmatic and asthmatic ASM cells.

Expression of connective tissue growth factor in asthmatic airway smooth muscle cells.

There is strong evidence to implicate transforming growth factor-beta in the remodeling that occurs in asthma, as levels are increased in bronchial lavage fluid and gene expression is increased in bronchial tissue. Transforming growth factor-beta is also known to increase the release of collagen from airway smooth muscle. Here we identify for the first time a possible mechanism for the effects of transforming growth factor-beta.