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Interleukin 1 signaling occurs exclusively via the type I receptor
Insights
The type II interleukin 1 (IL-1) receptor does not appear to transmit biological signals. Instead, even small amounts of the type I IL-1 receptor are sufficient for mediating all examined IL-1 actions.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Signaling
Background:
- Two receptors for the proinflammatory cytokine interleukin 1 (IL-1), type I and type II, have been identified.
- The signaling capacity of the type I IL-1 receptor is well-established.
- The precise function of the type II IL-1 receptor in IL-1 signaling remains unclear.
Purpose of the Study:
- To investigate whether the type II IL-1 receptor can transduce biological signals.
- To elucidate the role of the type II IL-1 receptor in cellular responses to IL-1.
Main Methods:
- Examined IL-1 responses in cells predominantly expressing the type II IL-1 receptor.
- Investigated IL-1 responses previously attributed to type II receptor mediation.
- Utilized a blocking antibody against the type II IL-1 receptor.
Main Results:
- IL-1 responses in both experimental settings were mediated by the type I IL-1 receptor.
- Blocking the type II IL-1 receptor did not inhibit, and sometimes enhanced, IL-1 responses.
- A minimal expression of type I IL-1 receptors sufficed for all tested IL-1 actions.
Conclusions:
- The type II IL-1 receptor is unlikely to be a primary signal transducer for IL-1.
- The type I IL-1 receptor is sufficient for mediating a wide range of IL-1 biological actions.
- The function of the type II IL-1 receptor may lie beyond direct signal transduction.
Abstract:
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.