Inflammatory cytokines regulate endothelial cell survival and tissue repair functions via NF-κB signaling

Abstract

Inflammation contributes to the development of fibrotic and malignant diseases. We assessed the ability of inflammatory cytokines to modulate endothelial cell survival and functions related to tissue repair/remodeling. Treatment with interleukin (IL)-1β or tumor necrosis factor (TNF)-α (2 ng/mL) led to human pulmonary artery endothelial cells becoming spindle-shaped fibroblast-like cells. However, immunoblot and DNA microarray showed no change in most endothelial and mesenchymal markers. In the presence of IL-1β or TNF-α, cells were resistant to apoptosis induced by deprivation of serum and growth factor, and were more migratory. In addition, cells treated with IL-1β or TNF-α contracted collagen gels more robustly. In contrast, transforming growth factor-β1 did not induce these responses. RNA interference targeting nuclear factor (NF)-κB p65 blocked the effects of IL-1β or TNF-α on cell morphologic change, survival, migration, and collagen gel contraction. These results suggest that endothelial cells may contribute to tissue repair/remodeling via the NF-κB signaling in a milieu of airway inflammation.

Keywords:

• NF-κB
• IL-1β
• TNF-α
• apoptosis
• tissue repair

Acknowledgment

The authors thank Ms Lillian Richards for the excellent secretarial support of this manuscript.

Disclosure

The authors report no conflicts of interest.