The role of tumor necrosis factor receptors in cell signaling and the significance of soluble form levels in the serum

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Abstract
Two types of tumor necrosis factor membrane receptors (TNF-R) have been identified, namely 55 and 75 kDa TNF-R. Soluble forms of these receptors are present in the human serum. Recent findings on the role of these two TNF-R in biological cell signaling and the clinical significance of the serum levels of soluble TNF-R (sTNF-R) were reviewed. It is not the uptake of TNF molecules into cells but rather the molecular capping of TNF-R on the cell membrane that initiates the biological activity of TNF. The 55 kDa TNF-R mediates major bioactivities of TNF, while the significance of 75 kDa TNF-R remains unclear. We herein suggest a new concept of the role of these two TNF-R: The 75 kDa TNF-R signal appeared to enhance that of 55 kDa TNF-R in the induction of ICAM-1 expression on HL-60 human promyelocytic leukemic cells. High serum levels of sTNF-R are reported in patients with malignancy, endotoxin shock, pneumonia, and autoimmune diseases. However, the source of elevated serum sTNF-R remains unclear. Studies on the clinical usefulness of serum sTNF-R levels as cancer and inflammation markers are now being carried out.