Interleukin-1-mediated febrile responses in mice and interleukin-1 beta activation of NFkappaB in mouse primary astrocytes, involves the interleukin-1 receptor accessory protein.

Abstract

The endogenous pyrogen interleukin-1 (IL-1) is considered as one of the key molecules in orchestrating the host response of injury and inflammation. IL-1 exerts its effects upon binding to the type I IL-1 receptor (IL-1RI). The IL-1-IL-1RI complex is further thought to associate with the IL-1 receptor accessory protein (IL-1RAcP), which is suggested to be important for most IL-1 signal transduction pathways. With the aim of investigating the importance of the IL-1RAcP in IL-1 signalling, IL-1alpha and IL-1beta induced febrile responses and IL-1beta-mediated activation of NFkappaB in primary astrocyte cultures were examined using IL-1RAcP-deficient (IL-1RAcP KO) and wild type mice, respectively. It was shown that neither recombinant rat IL-1alpha (rrIL-1alpha, 25 microg/kg), recombinant rat IL-1beta (rrIL-1beta, 40 microg/kg) nor recombinant human IL-1beta (rhIL-1beta, 50 microg/kg) injected i.p. could elicit febrile responses in the IL-1RAcP-deficient mice, while the same doses of rrIL-1alpha/beta or rhIL-1beta injected into wild type mice caused normal fever responses. A febrile response could be induced in the IL-1RAcP-deficient mice by i.p. administration of E. coli lipopolysaccharide (LPS, 50 microg/kg) and this response was similar to that obtained in wild type mice. Furthermore, it was shown that rhIL-1beta activated, in a concentration-dependent manner, nuclear translocation of the transcriptional nuclear factor kappa B (NFkappaB) in primary astrocyte cultures prepared from wild type mice, whereas no IL-1beta-induced translocation of NFkappaB could be detected in cultures prepared from IL-1RAcP-deficient mice, as revealed by electrophoretic mobility shift assay (EMSA). The rhIL-1beta-induced NFkappaB complexes were shown to contain p50 but no, or very little, p65 and cRel immunoreactive proteins.

• Authors: M Zetterström, J Lundkvist, D Malinowsky, G Eriksson, T Bartfai
• Journal: European cytokine network (Eur Cytokine Netw) Vol. 9 Issue 2 Pg. 131-8 (Jun 1998) ISSN: 1148-5493 [Print] France
• PMID: 9681388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL1RAP protein, human
• Il1rap protein, mouse
• Il1rap protein, rat
• Interleukin-1
• Interleukin-1 Receptor Accessory Protein
• NF-kappa B
• Proteins
• Receptors, Interleukin-1
• Recombinant Proteins

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Biological Transport (physiology)
• Cell Nucleus (metabolism)
• Cells, Cultured
• Fever (physiopathology)
• Humans
• Interleukin-1 (pharmacology, physiology)
• Interleukin-1 Receptor Accessory Protein
• Mice
• Mice, Mutant Strains
• NF-kappa B (metabolism)
• Proteins (physiology)
• Rats
• Receptors, Interleukin-1
• Recombinant Proteins (pharmacology)
• Signal Transduction (physiology)