Regionally specific induction of ICE mRNA and enzyme activity in the rat brain and adrenal gland by LPS

Tingsborg, Susanne; Zetterström, Maria; Alheim, Katarina; Hasanvan, Homa; Schultzberg, Marianne; Bartfai, Tamás

doi:10.1016/0006-8993(95)01525-6

Cited by 30 publications

(9 citation statements)

References 26 publications

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“…The parallel LPS-induced increases in reactive oxygen species production and caspase-1 activity observed here might indicate a causal interaction between these two parameters. The LPS-induced increase in caspase-1 activity is in contrast to a previous finding in which intraperitoneal injection of 2 mg/kg LPS (compared with 200 g used here) triggered caspase-1 activation in pituitary gland, but not in hippocampus or hypothalamus (38), although mRNA for caspase-1 was increased in all regions.…”

Section: Inhibition Of Caspase-1 Blocks Lps-induced Degenerative Chancontrasting

confidence: 55%

Lipopolysaccharide Inhibits Long Term Potentiation in the Rat Dentate Gyrus by Activating Caspase-1

Vereker¹,

Campbell²,

Roche

et al. 2000

Journal of Biological Chemistry

158

157

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Lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, may be responsible for at least some of the pathophysiological sequelae of bacterial infections, probably by inducing an increase in interleukin-1␤ (IL-1␤) concentration. We report that intraperitoneal injection of lipopolysaccharide increased hippocampal caspase-1 activity and IL-1␤ concentration; these changes were associated with increased activity of the stress-activated kinase c-Jun NH 2 -terminal kinase, decreased glutamate release, and impaired long term potentiation. The degenerative changes in hippocampus and entorhinal cortical neurones were consistent with apoptosis because translocation of cytochrome c and poly(ADP-ribose) polymerase cleavage were increased. Inhibition of caspase-1 blocked these changes, suggesting that IL-1␤ mediated the lipopolysaccharide-induced changes.There is increasing awareness of the existence of bidirectional communication between the immune and nervous systems. The proinflammatory cytokine, interleukin-1␤ (IL-1␤), 1 is one molecule that may play a pivotal role in integrating neuronal immune responses with those of the endocrine system because it exerts significant effects in all systems, for example in response to stressors such as infection. Gram-negative bacterial infections are associated with multiple pathophysiological changes; it is widely accepted that these changes are stimulated by lipopolysaccharide (LPS), a component of the outer membrane of most Gram-negative bacteria. These changes, which include fever, changes in sleep pattern, and anorexia (1), are mimicked by, and therefore thought to be mediated through production of, IL-1␤. Thus LPS, injected centrally or peripherally, increases IL-1␤ concentrations (2, 3) and IL-1␤ mRNA expression (4) in rat brain.Although it appears that in certain circumstances IL-1␤ may be neuroprotective, the consensus is that prolonged exposure, or exposure of tissue to high concentrations of IL-1␤, results in degenerative changes (5). Therefore it is significant that increased IL-1 concentrations in different brain areas have been correlated with neurodegenerative disorders such as Down syndrome, Alzheimer's disease (6), and Parkinson's disease (7), whereas in experimental models, IL-1␤ is considered to be responsible for the cell damage associated with ischemia (8) and excitotoxicity (9) and is increased after experimental traumatic lesions (10). A striking example of a neuronal deficit induced by IL-1␤ is the impairment in long term potentiation (LTP) in the hippocampus in vitro (11-13) and in vivo (14 -16).IL-1␤ is produced by glia (17, 18) and neurones (19,20) in response to tissue stress. It is cleaved from the inactive percursor, pro-IL-1␤, by the action of caspase-1, a member of a large family of cysteine proteases that have been implicated in apoptotic cell death (21-25). It might be predicted therefore that any trigger such as LPS, which induces an increase in IL-1␤, will do so by increasing activity of caspase-1.Our objective was to investigate th...

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Section: Inhibition Of Caspase-1 Blocks Lps-induced Degenerative Chancontrasting

confidence: 55%

Lipopolysaccharide Inhibits Long Term Potentiation in the Rat Dentate Gyrus by Activating Caspase-1

Vereker¹,

Campbell²,

Roche

et al. 2000

Journal of Biological Chemistry

158

157

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“…In the hippocampus, where no significant induction of caspase-1 mRNA could be detected by RT-PCR, there was a lower number of caspase-1 immunoreactive cells as compared to the amygdala and cortical regions (Eriksson et al, 1999). Other studies also show that caspase-1 and related caspases are constitutively expressed and induced by excitotoxic damage (Bhat et al, 1996;Tingsborg et al, 1996;Gillardon et al, 1997;Kinoshita et al, 1997).…”

Section: Discussionmentioning

confidence: 89%

“…The sequences for the PCR primers, with the annealing temperature and expected size of the PCR product in parentheses, were: 5'-CTCCATGAGCTTTGTACAAGG-3' (forward primer), and 5'-TGCTGATGTACCAGTTGGGG-3' (reverse primer), (54°C, 245 bp) corresponding to the nucleotides 550 -570 and 775-794, respectively, of the cDNA sequence for rat IL-1␤ (Chai et al, 1996), 5'-CACGTCTTG-CCCTCATTATC-3' (forward primer), and 5'CTGTCAGAA-GTCTTGTC-3' (reverse primer ) (51°C, 245 bp) corresponding to the nucleotides 482-501 and 664 -683, respectively, within the sequence coding for caspase-1 (Tingsborg et al, 1996); 5'-GACCCTGCAAGATGCAAGCC-3'(forward primer) and 5'GAGCGGATGAAGGTAAAGCG-3'(reverse primer) corresponding to the nucleotides 95-114 and 365-386 (accession no. M63101), respectively, of the rat IL-1ra cDNA sequence (Schultzberg et al, 1995) (53°C, 292 bp).…”

Section: Semi-quantitative Reverse Transcriptase-polymerase Chain Reamentioning

confidence: 99%

Increased expression of mRNA encoding interleukin-1? and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration

et al. 2000

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Kainic acid, an analogue of glutamate, injected systemically to rats evokes seizures that are accompanied by nerve cell damage primarily in the limbic system. In the present study, we have analyzed the temporal profile of the expression of the cytokines interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra), and the related IL-1beta-converting enzyme (ICE/caspase-1), in different regions of the rat brain in response to peripheral kainic acid administration (10 mg/kg, i.p.). In situ hybridization histochemistry experiments revealed that IL-1beta mRNA-expressing cells, morphologically identified as microglial cells, were mainly localized to regions showing pronounced neuronal degeneration; hippocampus, thalamus, amygdala, and certain cortical regions. The strongest expression of IL-1beta mRNA was observed after 12 hr in these regions. A weak induction of the IL-1beta mRNA expression was observed already at 2 hr. Similar results were obtained by RT-PCR analysis, showing a significantly increased expression of IL-1beta mRNA in the hippocampus and amygdala after 12 hr. In addition, RT-PCR analysis revealed that IL-1ra mRNA, and specifically mRNA encoding the secreted isoform of IL-1ra (sIL-1ra), was strongly induced in the hippocampus and amygdala at 12 and 24 hr post-injection. RT-PCR analysis of mRNA encoding caspase-1 showed a significantly increased expression in the amygdala after 12 hr. In conclusion, in response to systemic kainic acid injection IL-1beta mRNA is rapidly induced and followed by induction of IL-1ra mRNA and caspase-1 mRNA, supporting a role of the IL-1 system in the inflammatory response during excitotoxic damage.

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“…Therefore, one may predict, a priori, its presence within IL-1␤-ir cells. In fact, ICE mRNA expression has been demonstrated within the hypothalamus and within adrenal chromaffin cells of the rat suggesting the presence of this enzyme in neuronal cell types (Tinsborg et al, 1996). Furthermore, ICE has been localized immunocytochemically within neuronal cell bodies and fibers in the rat hypothalamus (Eriksson et al, 1999).…”

Section: Discussionmentioning

confidence: 95%

Interleukin-1? immunoreactivity in identified neurons of the rat magnocellular neurosecretory system: Evidence for activity-dependent release

Watt

Hobbs

2000

J. Neurosci. Res.

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Interleukin-1beta has been demonstrated in neurons of the rat hypothalamus, including cells of the magnocellular neurosecretory system and tuberoinfundibular system (Lechan et al., [1990] Brain Res. 514:135-140). Despite its potential importance to regulation of neuroendocrine function, however, neither the specific cell types that express interleukin-1beta or the conditions that may result in its release have yet been described. Therefore, we utilized a combination of immunocytochemical and immunoelectron microscopic localization, in conjunction with Western blot analysis, on normonatremic, hypernatremic, and lactating rats to assess the site of synthesis and potential secretion characteristics of interleukin-1beta in the rat magnocellular neurosecretory system. Interleukin-1beta immunoreactivity was localized within both oxytocin and vasopressin neurons in the paraventricular, supraoptic, accessory and periventricular hypothalamic nuclei. Additionally, interleukin-1beta immunoreactive fibers were localized in the zona interna and zona externa of the median eminence and in the neurohypophysis. Immunoelectron microscopic analysis revealed that interleukin-1beta immunoreactivity is associated with small spherical structures, distinct from neurosecretory granules, in neurosecretory axons within the neurohypophysis. Furthermore, stimulation of heightened neurosecretory activity via chronic osmotic challenge and lactation resulted in a marked diminution in levels of interleukin-1beta immunoreactivity in the neurohypophysis with a subsequent return to normal levels after cessation of the stimuli. Western blot analysis confirmed the existence of interleukin-1beta protein in the neurohypophysis and provided further evidence for reduction in levels of IL-1beta immunoreactivity after stimulation of secretory activity. These results suggest an endogenous neuronal source of interleukin-1beta exists within the rat magnocellular neurosecretory system under normal physiological conditions. The potential for activity-dependent release of IL-1beta and implications for the involvement of interleukin-1beta in regulation of neurosecretory activity are discussed.

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Regionally specific induction of ICE mRNA and enzyme activity in the rat brain and adrenal gland by LPS

Cited by 30 publications

References 26 publications

Lipopolysaccharide Inhibits Long Term Potentiation in the Rat Dentate Gyrus by Activating Caspase-1

Lipopolysaccharide Inhibits Long Term Potentiation in the Rat Dentate Gyrus by Activating Caspase-1

Increased expression of mRNA encoding interleukin-1? and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration

Interleukin-1? immunoreactivity in identified neurons of the rat magnocellular neurosecretory system: Evidence for activity-dependent release

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