Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit IL-1β activity but not binding: regulation of IL-1 responses is via type I receptor, not the accessory protein
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- Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit IL-1β activity but not binding: regulation of IL-1 responses is via type I receptor, not the accessory protein
- Do Young Yoon; C.A. Dinarello
- Bibliographic Citation
- Journal of Immunology, vol. 160, no. 7, pp. 3170-3179
- Publication Year
- The IL-1R accessory protein (IL-1RAcP) plays a role in IL-1R signaling by forming a complex with IL-1RI bound to the IL-1 ligand. We identified four hydrophilic peptide regions of the extracellular IL-1RAcP that may be available for complex formation (peptide 1, 71-83 domain I; peptide 2, 204- 211 domain II; peptide 3, 282-292 domain III; and peptide 4, 304-314 domain III). These peptides were synthesized, coupled to keyhole limpet hemocyanin and used to produce rabbit antisera. Each affinity-purified antiserum showed specificity for the respective peptide without cross-reacivity. Anti-peptide 2, 3, and 4 recognized surface expression of IL-1RAcP on the Th2 D10S cells by FACS and inhibited IL-1 driven proliferation. Anti-peptide 4 recognized intact IL-1RAcP and soluble IL-1RAcP. Anti-IL-1RAcP-peptide 4, which targets the terminal segment of domain III, inhibited 80% of IL-1β-driven proliferations of D10S cells. However, these IL-1RAcP Abs had no effect on the activity of human or mouse IL-1α. Whereas IL-1β down-regulated IL-1RI surface expression (p < 0.05), there was no change in the surface expression of IL-1RAcP. Moreover, murine IL-10 increased surface expression of IL-1RI, but did not affect expression of IL-1RAcP or the proliferation of D10S cells. Steady state levels of mRNA for IL-1RAcP and IL-1RI in D10S cells showed a similar pattern to that of surface expression of the respective receptors. We conclude that 1) blocking IL-1RAcP inhibits IL-1 signaling in D10S cells, 2) domains-II and III may be involved in complex formation with IL-1RI, 3) IL- 1RAcP is not regulated as is IL-1RI in the same cells, and 4) IL-1 responsiveness is dependent on the expression of IL-1RI, not IL-1RAcP.
- Amer Assoc Immunologists
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- 1. Journal Articles > Journal Articles
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