| 1. |
- Tingsborg, S, et al.
(author)
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Regionally specific induction of ICE mRNA and enzyme activity in the rat brain and adrenal gland by LPS.
- 1996
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In: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 712:1, s. 153-8
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Journal article (peer-reviewed)abstract
- Pro interleukin-1 beta converting enzyme (ICE) activity in the pituitary was found to be significantly increased 4 h after intraperitoneal injection of E. coli lipopolysaccharides, when distribution and inducibility of the enzyme was studied in the adult rat brain and the adrenal gland, using an artificial fluorescence peptide substrate. The same lipopolysaccharide treatment induced ICE mRNA levels in the pituitary, adrenal gland and hypothalamus as studied by reverse transcript-polymerase chain reaction.
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| 2. |
- Lundkvist, J, et al.
(author)
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Acute-phase responses in transgenic mice with CNS overexpression of IL-1 receptor antagonist.
- 1999
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In: American Journal of Physiology. - 0002-9513 .- 2163-5773. ; 276:3 Pt 2, s. R644-51
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Journal article (peer-reviewed)abstract
- The interleukin-1 (IL-1) receptor antagonist (IL-1ra) is an endogenous antagonist that blocks the effects of the proinflammatory cytokines IL-1alpha and IL-1beta by occupying the type I IL-1 receptor. Here we describe transgenic mice with astrocyte-directed overexpression of the human secreted IL-1ra (hsIL-1ra) under the control of the murine glial fibrillary acidic protein (GFAP) promoter. Two GFAP-hsIL-1ra strains have been generated and characterized further: GILRA2 and GILRA4. These strains show a brain-specific expression of the hsIL-1ra at the mRNA and protein levels. The hsIL-1ra protein was approximated to approximately 50 ng/brain in cytosolic fractions of whole brain homogenates, with no differences between male and female mice or between the two strains. Furthermore, the protein is secreted, inasmuch as the concentration of hsIL-1ra in the cerebrospinal fluid was 13 (GILRA2) to 28 (GILRA4) times higher in the transgenic mice than in the control animals. To characterize the transgenic phenotype, GILRA mice and nontransgenic controls were injected with recombinant human IL-1beta (central injection) or lipopolysaccharide (LPS, peripheral injection). The febrile response elicited by IL-1beta (50 ng/mouse icv) was abolished in hsIL-1ra-overexpressing animals, suggesting that the central IL-1 receptors were occupied by antagonist. The peripheral LPS injection (25 micrograms/kg ip) triggered a fever in overexpressing and control animals. Moreover, no differences were found in LPS-induced (100 and 1,000 micrograms/kg ip; 1 and 6 h after injection) IL-1beta and IL-6 serum levels between GILRA and wild-type mice. On the basis of these results, we suggest that binding of central IL-1 to central IL-1 receptors is not important in LPS-induced fever or LPS-induced IL-1beta and IL-6 plasma levels.
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