Satoru Nakai

Interleukin-1β inhibits long-term potentiation in the CA3 region of mouse hippocampal slices

The effect of recombinant human interleukin 1-beta (IL-1 beta) on long-term potentiation (LTP) in the mossy fiber-CA3 pathway of mouse hippocampal slice preparations was investigated. IL-1 beta significantly inhibited LTP in concentrations as low as 2.9 pM (50 pg/ml). This effect of IL-1 beta was blocked by concurrent application of 100 nM Lys-D-Pro-Thr, a tripeptide analogue of IL-1 beta. This is the first evidence that IL-1 beta can regulate LTP of synaptic transmission in the hippocampus.

Immobilization stress induces interleukin-1β mRNA in the rat hypothalamus

Abstract Immobilization stress induced interleukin-1β (IL-1β) mRNA in the rat hypothalamus. IL-1β mRNA was induced at 30 min after the start of immobilization, reached a maximum at 60 min and then was still detected with a decreased level at 120 min. However, 240 min after the start of the immobilization, IL-1β mRNA became hardly detectable despite the continuance of immobilization. Distinct expression of IL-1β mRNA was not detected in any other brain region examined at 30 and 60 min after the start of immobilization. These results demonstrate that the immobilization stress induces the expression of IL-1β mRNA solely in the hypothalamus and suggest that IL-1β is involved in the response to stress there.

Convulsants induce interleukin-1β messenger RNA in rat brain

Abstract The effects of systemic administration of kainic acid and pentylenetetrazol on interleukin-1β gene expression in the rat brain was studied. After the administration of kainic acid in a convulsive dose (10 mg/kg i.p.), Interleukin-1β mRNA was induced intensely in the cerebral cortex, thalamus and hypothalamus, moderately in the hippocampus and weakly in the striatum, but not in the midbrain, pons-medulla and cerebellum. Pentylenetetrazol induced Interleukin-1β mRNA in the cerebral cortex, hypothalamus, and hippocampus with a faster time-course than kainic acid. Diazepam suppressed both the convulsion and the induction of Interleukin-1β mRNA produced by kainic acid. Dexamethasone suppressed the induction of Interleukin-1β mRNA, but did neither the convulsion nor the induction of c-fos mRNA following the injection of kainic acid. These results provide the first evidence that intensive neuronal excitation induces Interleukin-1β mRNA in particular regions of the brain.

cDNA cloning of IL-1α and IL-1β from mRNA of U937 cell line

Clones of cDNAs encoding growth inhibitory factors for human melanoma cell line A375 were isolated from cDNA library prepared by using mRNA derived from human histiocytic lymphoma cell line U937 induced with PMA and further stimulated with LPS. Cloning was achieved using Okayama-Berg cDNA expression vector system that permits expression of the inserted cDNA segments in mammalian cells. By assaying the transfected COS-1 cells supernatants and cell extracts, we isolated two distinct cDNA clones encoding growth inhibitory factors. It was determined by the nucleotide sequences of the inserts, the cDNAs corresponded to IL-1 alpha and -1 beta. Our results indicate U937 cells can be induced to produce both interleukin-1s.

A simple, sensitive bioassay for the detection of interleukin-1 using human melanoma A375 cell line

Interleukin-1 (IL-1) exhibits multiple biological properties on various tissues by modulating immunologic, inflammatory, metabolic, and neurologic functions. Considerable attention has focussed on the measurement of IL-1 activity. We reported a simple, sensitive, and specific bioassay for IL-1 using human melanoma A375 subclone which is highly sensitive for the cell growth inhibitory activity of IL-1. This bioassay method is allows detection of as low as 10pg of IL-1 beta/ml or 30pg of IL-1 alpha/ml. Since this A375 subclone cell dose not respond to prostaglandin E2 plant lectins, lipopolysaccharide, and cytokines such as interleukin-2, interleukin-6, tumor necrosis factor, interferon or colony-stimulating factor, it is an extremely useful and rapid method for the measurement of IL-1 activity in a variety of experimental and clinical conditions. The assay method was used in the presence of antisera to IL-1 beta to discriminate two species of IL-1, IL-1 alpha and IL-1 beta, produced in human peripheral mononuclear cells.

Purification and characterization of recombinant human interleukin-1β produced in Escherichia coli

Summary Recombinant human interleukin-1 β (rIL-1 β ) produced in Escherichia coli was purified to homogeneity by a combination of mass ion exchange column chromatography, ion exchange and gel filtration high performance liquid chromatography. The purified rIL-1 β had a molecular weight of 18 kD on SDS-polyacrylamide gel electrophoresis and an isoelectric point of 6.9 on analytical isoelectric focusing. These values were almost same as those of natural interleukin-1 β . The amino acid composition and amino acid sequence of the amino terminal region were consistent with those deduced from the cDNA sequence. In addition, the primary structure was confirmed by peptide mapping with lysyl-endopeptidase on reverse phase HPLC. Besides rIL-1 β with amino terminal Ala, two molecular species, [Met 0 ]rIL-1 β and [desAla 1 ]rIL-1 β , were also obtained. Biological and physicochemical properties of the three species of rIL-1 β were compared.

Methamphetamine-induced expression of interleukin-1β mRNA in the rat hypothalamus

The effect of methamphetamine on the expression of interleukin-1 beta (IL-1 beta) mRNA in the rat brain was investigated with Northern blot analysis. Methamphetamine (2-15 mg/kg, i.p.) caused a marked induction of IL-1 beta mRNA in the hypothalamus among the 8 brain regions examined, in a dose-dependent manner. The level of IL-1 beta mRNA reached a maximum at 1 h and rapidly declined within 2 h after the injection of 15 mg/kg. These results provide the first evidence that methamphetamine induces the expression of IL-1 beta mRNA in the hypothalamus, which may be partly involved in the production of central actions of this drug.

EFFECT OF BONE MARROW TRANSPLANTATION ON ANTI-PHOSPHOLIPID ANTIBODY SYNDROME IN MURINE LUPUS MICE

The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels.

Dexamethasone regulation of the expression of cytokine mRNAs induced by interleukin-1 in the astrocytoma cell line U373MG

BSF‐2/IL‐6, GM‐CSF and IL‐1β mRNAs were induced by recombinant IL‐1 in human astrocytoma cell line U373MG. The induction of BSF‐2/IL‐6 and IL‐1β mRNAs did not require de novo protein synthesis while that of GM‐CSF mRNA required a newly synthesized protein. Dexamethasone inhibited the induction of these cytokine mRNAs by IL‐1. This process seems to require continued protein synthesis. These results suggest that the production of these cytokines are positively and negatively controlled by IL‐1 and glucocorticoids, respectively, in astrocytes.

Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone.

Catalepsy and changes in striatal and limbic dopamine metabolism were investigated in mice after oral administration of aripiprazole, haloperidol, and risperidone. Catalepsy duration decreased with chronic (21 day) aripiprazole compared with acute (single dose) treatment across a wide dose range, whereas catalepsy duration persisted with chronic haloperidol treatment. At the time of maximal catalepsy, acute aripiprazole did not alter neostriatal dopamine metabolite/dopamine ratios or homovanillic acid (HVA) levels, and produced small increases in dihydroxyphenylacetic acid (DOPAC). Effects were similar in the olfactory tubercle. Dopamine metabolism was essentially unchanged in both regions after chronic aripiprazole. Acute treatments with haloperidol or risperidone elevated DOPAC, HVA, and metabolite/dopamine ratios in both brain areas and these remained elevated with chronic treatment. The subtle effects of aripiprazole on striatal and limbic dopamine metabolism, and the decrease in catalepsy with chronic administration, illustrate fundamental differences in dopamine neurochemical actions and behavioral sequelae of aripiprazole compared to haloperidol or risperidone.