Detection of lnterleukin-1 Bioactivity in Various Brain Regions of Normal Healthy Rats

Quan, Ning; Zhang, Zhaobin; Emery, Milburn S.; Bonsall, Robert W.; Weiss, Jay M.

doi:10.1159/000097226

Cited by 44 publications

(19 citation statements)

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“…Here, we show that antagonizing IL-1R1 using IL-1ra bi-directionally modulates sIPSCs, indicating that the receptor plays an important tonic role in regulating spontaneous GABAergic transmission in the CeA through pre- and postsynaptic mechanisms. Indeed, active IL-1β can be detected under basal conditions in the brain 63 , and there is evidence for a physiological role of IL-1β in modulating excitability and neurotransmission to regulate memory formation and sleep 64–68 . Additionally, IL-1β signaling is associated with anxiety and depression 69–72 , and it is possible that changes in IL-1R1’s modulation of basal neurotransmission in the CeA could contribute to the expression of these disorders.…”

Section: Discussionmentioning

confidence: 99%

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Patel

Khom

Steinman

et al. 2019

Brain, Behavior, and Immunity

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The interleukin-1 system (IL-1) is a prominent pro-inflammatory pathway responsible for the initation and regulation of immune responses. Human genetic and preclinical studies suggest a critical role for IL-1β signaling in ethanol drinking and dependence, but little is known about the effects of chronic ethanol on the IL-1 system in addiction-related brain regions such as the central amygdala (CeA). In this study, we generated naïve, non-dependent (Non-Dep) and dependent (Dep) male mice using a paradigm of chronic-intermittent ethanol vapor exposure interspersed with two-bottle choice to examine 1) the expression of IL-1β, 2) the role of the IL-1 system on GABAergic transmission, and 3) the potential interaction with the acute effects of ethanol in the CeA. Immunohistochemistry with confocal microscopy was used to assess expression of IL-1β in microglia and neurons in the CeA, and whole-cell patch clamp recordings were obtained from CeA neurons to measure the effects of IL-1β (50 ng/ml) or the endogenous IL-1 receptor antagonist (IL-1ra; 100 ng/ml) on action potential-dependent spontaneous inhibitory postsynaptic currents (sIPSCs). Overall, we found that IL-1β expression is significantly increased in microglia and neurons of Dep compared to Non-Dep and naïve mice, IL-1β and IL-1ra bi-directionally modulate GABA transmission through both pre- and postsynaptic mechanisms in all three groups, and IL-1β and IL-1ra do not alter the facilitation of GABA release induced by acute ethanol. These data suggest that while ethanol dependence induces a neuroimmune response in the CeA, as indicated by increased IL-1β expression, this does not significantly alter the neuromodulatory role of IL-1β on synaptic transmission.

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Section: Discussionmentioning

confidence: 99%

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Patel

Khom

Steinman

et al. 2019

Brain, Behavior, and Immunity

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“…These pro-inflammatory cytokines are produced constitutively at low to nondetectable levels [35][36][37]. The expression of IL-1, IL-6 and TNF can be transiently induced in a variety of cells and by various stimuli [38].…”

Section: Cytokines and Their Pathwaysmentioning

confidence: 99%

Regulation of Multidrug Resistance by Pro-Inflammatory Cytokines

Piquette-Miller²

2006

CCDT

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Various mechanisms have been implicated in the development of resistance of cancer cells to chemotherapy. Multidrug resistance (MDR) is a phenomenon in which cancer cells are resistant to the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. One major mechanism by which this occurs is through the over-expression of ATP-dependent drug efflux transporters such as the P-glycoprotein (PGP) and multidrug resistance-associated protein (MRP). Regulation of MDR can occur at many levels including transcriptional, mRNA, protein and post-translational. In recent years it has been demonstrated that alterations in the expression and activity of the MDR transporters are seen in numerous tissues during an inflammatory response. An acute inflammatory response is associated with many conditions including infection, injury, hypoxia and stress and is known to result in the induction of several pro-inflammatory cytokines. Whether the function of cytokines can be harnessed in overcoming drug resistance of tumors has yet to be examined and explored. In this review, we will focus on the various studies investigating the regulation of MDR during an inflammatory response, in particular by cytokines. The mediators and pathways involved as well as the possible mechanisms of MDR regulation will be discussed. It is hoped that by understanding the clinical importance of inflammatory mediators in MDR, new doors will open and future insights will lead to the development of novel immunotherapeutics for the treatment of cancer.

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“…However, IL-1β mRNA and protein are now known to be expressed by numerous other cell types, suggesting a broader function beyond the immune system. In the normal central nervous system (CNS), for example, all components of the IL-1 signal transduction system appear to be present (Farrar et al, 1987; Breder et al, 1988; Takao et al, 1990; Quan et al, 1996; Loddick et al, 1997; Schneider et al, 1998; French et al, 1999; Hammond et al, 1999; Huitinga et al, 2000; Toyooka et al, 2003). Moreover, several studies have provided evidence for diurnal or rapid, activity-dependent release of IL-1β from neurons (Tringali et al, 1996; Tringali et al, 1997; Watt and Hobbs, 2000; Hailer et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Neuromodulatory role of endogenous interleukin-1β in acute seizures: Possible contribution of cyclooxygenase-2

Claycomb¹,

Hewett²,

Hewett³

2012

Neurobiology of Disease

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The function of endogenous interleukin-1β (IL-1β) signaling in acute seizure activity was examined using transgenic mice harboring targeted deletions in the genes for either IL-1β (Il1b) or its signaling receptor (Il1r1). Acute epileptic seizure activity was modeled using two mechanistically distinct chemoconvulsants, kainic acid (KA) and pentylenetetrazole (PTZ). KA-induced seizure activity was more severe in homozygous null (-/-) Il1b mice compared to their wild-type (+/+) littermate controls, as indicated by an increase in the incidence of sustained generalized convulsive seizure activity. In the PTZ seizure model, the incidence of acute convulsive seizures was increased in both Il1b and Il1r1 -/- mice compared to their respective +/+ littermate controls. Interestingly, the selective cyclooxygenase (COX)-2 inhibitor, rofecoxib, mimicked the effect of IL-1β deficiency on PTZ-induced convulsions in Il1r1 +/+ but not -/- mice. Together, these results suggest that endogenous IL-1β possesses anticonvulsive properties that may be mediated by arachidonic acid metabolites derived from the catalytic action of COX-2.

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Detection of lnterleukin-1 Bioactivity in Various Brain Regions of Normal Healthy Rats

Cited by 44 publications

References 0 publications

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Regulation of Multidrug Resistance by Pro-Inflammatory Cytokines

Neuromodulatory role of endogenous interleukin-1β in acute seizures: Possible contribution of cyclooxygenase-2

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