Endothelial Cell Contact Potentiates Release of Soluble Tumor Necrosis Factor (TNF) Receptors from the Monocyte-like Cell Line THP-1

Abstract

The two tumor necrosis factor (TNF) receptors can undergo proteolytic cleavage to form soluble receptors, TNF-R55-BP and TNF-R75-BP, that can neutralize TNF. The aim was to study the release of soluble TNF receptor forms during monocyte-endothelial cell interaction. Monocytic THP-1 cells were used, and their release of TNF-R75-BP was determined. Contact between THP-1 cells and confluent endothelial cells induced fourfold higher release of TNF-R75-BP from the THP-1 cells than with these cells in suspension. The release was further increased up to eightfold after prestimulation of the endothelial cells with interleukin-1 β ( IL -1 β). Prestimulation for 10 min gave maximal release of TNF-R75-BP from the attached THP-1 cells. IL-1β by itself did not induce shedding of soluble TNF receptors in THP-1 cells. Blocking antibodies against the endothelial cell adhesion molecules VCAM, ICAM, and E-selectin did not affect the release of TNF-R75-BP from THP-1 cells attached to the endothelium. Conditioned medium from IL-1β-stimulated endothelial cells increased the production of TNF-R75-BP from THP-1 cells in suspension. However, surface contact between endothelial cells and THP-1 cells was necessary for maximal production of TNF-R75-BP. TNF-α released from endothelial cells on IL-1β stimulation did not promote shedding of TNF-R75 from THP-1 cells. Thus, endothelial cell contact potentiates the production of TNF-R75-BP in a monocyte-like cell line. The shedding of soluble TNF receptors observed in this case seems to be a result of both cell attachment and soluble factors.