Ezrin/radixin/moesin proteins are phosphorylated by TNF-alpha and modulate permeability increases in human pulmonary microvascular endothelial cells.

Endothelial cells (ECs) respond to TNF-alpha by altering their F-actin cytoskeleton and junctional permeability through mechanisms that include protein kinase C (PKC) and p38 MAPK. Ezrin, radixin, and moesin (ERM) regulate many cell processes that often require a conformational change of these proteins as a result of phosphorylation on a conserved threonine residue near the C terminus. This study tested the hypothesis that ERM proteins are phosphorylated on this critical threonine residue through TNF-alpha-induced activation of PKC and p38 and modulate permeability increases in pulmonary microvascular ECs.

Sulindac sulfone is most effective in modulating beta-catenin-mediated transcription in cells with mutant APC.

Sulindac sulfone (FGN-1, Aptosyn), a metabolite of the nonsteroidal anti-inflammatory drug sulindac, lacks cyclooxygenase inhibitory activity. Although its ability to inhibit tumorigenesis in both carcinogen-treated animals and patients with familial adenomatous polyposis has been attributed to the induction of apoptosis, its complete mechanism of action remains unclear. The purpose of the present study was to determine the ability of sulindac metabolites to regulate cellular levels of beta-catenin and downstream targets of the adenomatous polyposis coli (APC)/beta-catenin pathway in vitro.

Activation of SRC tyrosine kinases in response to ICAM-1 ligation in pulmonary microvascular endothelial cells.

Previous studies demonstrated that ICAM-1 ligation on human pulmonary microvascular endothelial cells (ECs) sequentially induces activation of xanthine oxidase and p38 MAPK. Inhibition of these signaling events reduces neutrophil migration to the EC borders. This study examined the role of SRC tyrosine kinases in ICAM-1-initiated signaling within these ECs.

Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation.

Neutrophil adherence to tumor necrosis factor-alpha (TNF-alpha)-treated human pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)-dependent signaling events. This study determined whether similar changes occurred in rat PMECs and whether rat pulmonary arterial endothelial cells (PAECs) responded differently. Neutrophil adherence induced an increase in the formation of F-actin and in the apparent stiffness of TNF-alpha-treated rat PMECs.