Expression of the types A and B tumor necrosis factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-kappa B. TNF alpha is not needed for induction of a biological effect via TNF receptors.
The expression and biological function of the types A and B tumor necrosis factor (TNF) receptors were studied using three cell types. SW480T, HEp2, and HL60 cells had, respectively, mainly the type A, only the type B, and roughly similar amounts of both receptors. Dibutyric cAMP treatment induced a 3-6-fold increase in the amount of the type A receptor in HL60 cells without affecting the amount of the type B receptor. Expression of both receptors can thus be regulated independently. HEp2 and human umbilical vein endothelial cells only showed the type B receptor, and expression of the type A receptor could not be induced in these cells. HL60 cells showed, upon Scatchard analysis, a single binding site for TNF alpha, and its Kd may correspond to that of the type A receptor. The approximately 7-fold lower affinity of TNF alpha binding to the type B receptor of HL60 cells was only detected after blocking all TNF alpha binding to the type A receptor. Both the types A and B receptors mediated TNF alpha-induced activation of the transcription factor NF-kappa B. The agonistic antibody htr9 to the type B receptor also activated NF-kappa B. Thus, signal transduction via the type B receptor may only require interaction with the receptor's extracellular domain.
Hohmann
H P
HP
Central Research Units, Hoffmann-La Roche Ltd., Basel, Switzerland.
Brockhaus
M
M
Baeuerle
P A
PA
Remy
R
R
Kolbeck
R
R
van Loon
A P
AP
D000911:Antibodies, Monoclonal; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine