Interleukin 1 signaling occurs exclusively via the type I receptor.
Two receptors for the proinflammatory cytokine interleukin 1 (IL-1) have been cloned and characterized biochemically. While it has been well established that the type I (80-kDa) IL-1 receptor can mediate responses to IL-1, the function of the type II (60-kDa) IL-1 receptor has been unknown. In this manuscript we describe experiments designed to ask whether the type II receptor is capable of delivering a biological signal. We have examined two types of experimental situation: responses to IL-1 in cells which express predominantly the type II receptor, and responses to IL-1 which have been suggested previously in the literature to be mediated by type II receptors. In both situations we find that the responses instead are mediated via type I receptors. A blocking antibody against the type II receptor never inhibits, and in fact sometimes enhances, the responses. We conclude that a very small number of type I receptors is sufficient to mediate all of the actions of IL-1 which we have examined here and that the function of the type II receptor may not be to transduce signals.
Sims
J E
JE
Department of Molecular Biology, Immunex Research and Development Corporation, Seattle, WA 98101.
Gayle
M A
MA
Slack
J L
JL
Alderson
M R
MR
Bird
T A
TA
Giri
J G
JG
Colotta
F
F
Re
F
F
Mantovani
A
A
Shanebeck
K
K
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1