Inhibition of interleukin-1 responsiveness by type II receptor gene transfer

A surface "Receptor" with anti-interleukin-1 function

Fabio Re, Marina Sironi, Marta Muzio, Cristian Matteucci, Martino Introna, Simone Orlando, Giselle Penton-Rol, Steven K. Dower, John E. Sims, Francesco Colotta, Alberto Mantovani

Research output: Contribution to journalArticle

85 Citations (Scopus)

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 NFkB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1β. 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-1. Cells transfected with the 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 anti-inflammatory signals, whose only known function is to capture and block IL-1.

Original languageEnglish
Pages (from-to)1841-1850
Number of pages10
JournalJournal of Experimental Medicine
Volume183
Issue number4
Publication statusPublished - Apr 1 1996

Fingerprint

Interleukin-1 Type II Receptors
Interleukin-1
Genes
Blocking Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Inhibition of interleukin-1 responsiveness by type II receptor gene transfer : A surface "Receptor" with anti-interleukin-1 function. / Re, Fabio; Sironi, Marina; Muzio, Marta; Matteucci, Cristian; Introna, Martino; Orlando, Simone; Penton-Rol, Giselle; Dower, Steven K.; Sims, John E.; Colotta, Francesco; Mantovani, Alberto.

In: Journal of Experimental Medicine, Vol. 183, No. 4, 01.04.1996, p. 1841-1850.

Research output: Contribution to journalArticle

Re, F, Sironi, M, Muzio, M, Matteucci, C, Introna, M, Orlando, S, Penton-Rol, G, Dower, SK, Sims, JE, Colotta, F & Mantovani, A 1996, 'Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: A surface "Receptor" with anti-interleukin-1 function', Journal of Experimental Medicine, vol. 183, no. 4, pp. 1841-1850.
Re, Fabio ; Sironi, Marina ; Muzio, Marta ; Matteucci, Cristian ; Introna, Martino ; Orlando, Simone ; Penton-Rol, Giselle ; Dower, Steven K. ; Sims, John E. ; Colotta, Francesco ; Mantovani, Alberto. / Inhibition of interleukin-1 responsiveness by type II receptor gene transfer : A surface "Receptor" with anti-interleukin-1 function. In: Journal of Experimental Medicine. 1996 ; Vol. 183, No. 4. pp. 1841-1850.
@article{8eccde6339004893b6e487ecb38deba7,
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 NFkB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1β. 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-1. Cells transfected with the 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 anti-inflammatory signals, whose only known function is to capture and block IL-1.",
author = "Fabio Re and Marina Sironi and Marta Muzio and Cristian Matteucci and Martino Introna and Simone Orlando and Giselle Penton-Rol and Dower, {Steven K.} and Sims, {John E.} and Francesco Colotta and Alberto Mantovani",
year = "1996",
month = "4",
day = "1",
language = "English",
volume = "183",
pages = "1841--1850",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Inhibition of interleukin-1 responsiveness by type II receptor gene transfer

T2 - A surface "Receptor" with anti-interleukin-1 function

AU - Re, Fabio

AU - Sironi, Marina

AU - Muzio, Marta

AU - Matteucci, Cristian

AU - Introna, Martino

AU - Orlando, Simone

AU - Penton-Rol, Giselle

AU - Dower, Steven K.

AU - Sims, John E.

AU - Colotta, Francesco

AU - Mantovani, Alberto

PY - 1996/4/1

Y1 - 1996/4/1

N2 - 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 NFkB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1β. 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-1. Cells transfected with the 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 anti-inflammatory signals, whose only known function is to capture and block IL-1.

AB - 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 NFkB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1β. 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-1. Cells transfected with the 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 anti-inflammatory signals, whose only known function is to capture and block IL-1.

UR - http://www.scopus.com/inward/record.url?scp=0029924136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029924136&partnerID=8YFLogxK

M3 - Article

VL - 183

SP - 1841

EP - 1850

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 4

ER -