title: Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: a surface "receptor" with anti-interleukin-1 function.
abstract: The hypothesis that the type II receptor (RII) acts as a decoy for interleukin-1 (IL-1) was tested by gene transfer in cells expressing only the type I receptor (8387 fibroblasts). RII-transfected cells showed defective responsiveness to IL-1 in terms of NFkappaB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1 beta. Hence defective IL-1 responsiveness of RII-transfected cells requires surface expression of the molecule. RII-transfected cells showed normal responsiveness to TNF, which shares functional properties and elements in the signal transduction pathway with IL-1. Cells transfected with a deletion mutant of RII missing 26 of 29 amino acids of the cytoplasmic portion of the molecule showed impaired responsiveness to IL-2. Cells transfected with full-length or the cytoplasmic deletion mutant of RII released copious amounts of RII in the supernatant. However, transfected cells showed defective responsiveness to brief exposure to IL-1, in the absence of measurable released RII. These results indicate that impairment of the responsiveness to IL-1 following RII gene transfer was dependent upon surface expression of the molecule, specific for IL-1 and unaffected by truncation of the cytoplasmic portion. Thus, the type II "receptor" is a decoy surface molecule, regulated by antiinflammatory signals, whose only known function is to capture and block IL-1.
authors.affiliation: Istituto Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Re
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: M
authors.initials: M
authors.lastname: Muzio
authors.forename: C
authors.initials: C
authors.lastname: Matteucci
authors.forename: M
authors.initials: M
authors.lastname: Introna
authors.forename: S
authors.initials: S
authors.lastname: Orlando
authors.forename: G
authors.initials: G
authors.lastname: Penton-Rol
authors.forename: S K
authors.initials: SK
authors.lastname: Dower
authors.forename: J E
authors.initials: JE
authors.lastname: Sims
authors.forename: F
authors.initials: F
authors.lastname: Colotta
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D001483:Base Sequence; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D015398:Signal Transduction; D014162:Transfection
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II