A novel role of interleukin-1-converting enzyme in cytokine-mediated inducible nitric oxide synthase gene expression: Implications for neuroinflammatory diseases

Jüttler, Eric; Bonmann, Eckhard; Spranger, Matthias; Kolb-Bachofen, Victoria; Suschek, Christoph V.

doi:10.1016/j.mcn.2007.01.004

Cited by 16 publications

(7 citation statements)

References 38 publications

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“…This finding endorses reports that IL-1β is associated with host resistance, showing that the inflammasome is activated in response to Leishmania infection [28]. It also corroborates previous reports of inflammasome activation being critical for the control of L. amazonensis, L. braziliensis, and L. infantum chagasi replication in vivo [29].…”

Section: Plos Onesupporting

confidence: 92%

Cytokine profile in Leishmania-positive blood donors

et al. 2020

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Serum levels of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17 (IL-17), interferon gamma (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β), cytokines involved in the immune response, were investigated in 75 Leishmania-positive blood donors living in endemic areas. Based on their status in 2011 and 2015, the subjects were clustered into three groups: positive for at least one diagnostic method in both years, but lacking clinical progression to disease (G1); positive on at least one method in 2011 but negative in 2015 (G2); negative on all methods in both years (G3). Donors were interviewed for sociodemographic data collection and underwent clinical evaluation and laboratory tests. Serum cytokines were quantified using a CBA Flex set (BD Biosciences). Significant differences were found for all the cytokines evaluated, with lower concentrations in consistently Leishmania-negative individuals. The exception was IFN-γ, with similar levels among all donors. No changes consistent with active disease were observed in the laboratory results for Leishmania-positive donors who underwent clinical evaluation, none of whom progressed to disease. This suggests that infection control is associated with serum IL-17 levels. Resolution of Leishmania infection in positive donors may be related to high levels of IL-17 and low levels of IL-10, highlighting the role played by IL-17 in asymptomatic Leishmania-infected individuals.

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Section: Plos Onesupporting

confidence: 92%

Cytokine profile in Leishmania-positive blood donors

et al. 2020

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“…The impact of caspase 1 over-expression on tissue destruction has been demonstrated in a brain ischemia injury model where blocking caspase 1 expression resulted in a decreased infarct size (Sifringer et al, 2007). Caspase 1 regulated over-production of the cleaved, bioactive form of IL-1β results in up-regulation of nitric oxide synthase (iNOS or NOS2) expression and, thus, causes increased production of nitric oxide (NO) (Juttler et al, 2007). The cell primarily responsible for the iNOS-induced release of NO is the activated glial cell.…”

Section: Discussionmentioning

confidence: 99%

Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice

et al. 2012

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Lead (Pb) was one of the first poisons identified, and the developing nervous system is particularly vulnerable to its toxic effects. Relatively low, subclinical doses, of Pb that produce no overt signs of encephalopathy can affect cognitive, emotional, and motor functions. In the present study, the effects of developmental Pb-exposure on behavioral performance and gene expression in BALB/cAnNTac mice were evaluated. Pups were exposed to Pb from gestational-day (gd) 8 to postnatal-day (pnd) 21 and later evaluated in exploratory behavior, rotarod, Morris water maze, and resident-intruder assays as adults. Pb-exposure caused significant alterations in exploratory behavior and water maze performance during the probe trial, but rotarod performance was not affected. Pb-exposed males displayed violent behavior towards their cage mates, but not to a stranger in the resident-intruder assay. Gene expression analysis at pnd21 by microarray and qRT-PCR was performed to provide a molecular link to the behavior changes that were observed. Pb strongly up-regulated gene expression within the signaling pathways of mitogen activated protein kinases (MAPKs), extra-cellular matrix (ECM) receptor, focal adhesion, and vascular endothelial growth-factor (VEGF), but Pb down-regulated gene expression within the pathways for glycan structures-biosynthesis 1, purine metabolism, and N-glycan biosynthesis. Pb increased transcription of genes for major histocompatibility (MHC) proteins, the chemokine Ccl28, chemokine receptors, IL-7, IL7R, and proteases. The qRT-PCR analysis indicated an increase of gene expression in the whole brain for caspase 1 and NOS2. Analysis of IL-1β, caspase 1, NOS2, Trail, IL-18 and IL-33 gene expression of brain regions indicated that Pb perturbed the inter-regional expression pattern of pro-inflammatory genes. Brain region protein concentrations for IL-10, an anti-inflammatory cytokine, showed a significant decrease only within the cortex region. Results indicate that Pb differentially affects the behavior of male and female mice in that females did less exploration and the males were selectively more aggressive. Gene expression data pointed to evidence of neuroinflammation in the brain of both female and male mice. Pb had more of an effect in the males on expression of vomeronasal receptor genes associated with odor detection and social behavior.

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“…Caspase-1 promotes the release of IL-1␤ and IL-18, which in turn can activate iNOS (25). In fact, it was recently shown that IFN-␥-and TNF-␣-induced iNOS activation in astrocytes and cerebral endothelial cells is dependent on caspase-1-mediated IL-1␤ secretion (38). However, our data show that neutralization of IL-1␤ and/or IL-18 with specific antibodies resulted in a rather increased iNOS expression by FLA-BSDot, ruling out the requirement for these cytokines in flagellin-mediated iNOS up-regulation (Fig.…”

Section: Discussionmentioning

confidence: 99%

A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes

Buzzo

Campopiano

Massis

et al. 2010

Journal of Biological Chemistry

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Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1␤/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to clear infections, little is known about the relative anti-pathogen effector mechanisms operating through each of them. Here we show that the cytosolic flagellin (FLA-BSDot) was able to activate iNOS, an enzyme previously associated with TLR5 pathway. Using Nlrc4-or Naip5-deficient macrophages, we found that both receptors are involved in iNOS activation by FLA-BSDot. Moreover, distinct from extracellular flagellin (FLA-BS), iNOS activation by intracellular flagellin is completely abrogated in the absence of caspase-1. Interestingly, IL-1␤ and IL-18 do not seem to be important for FLA-BSDot-mediated iNOS production. Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS.

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A novel role of interleukin-1-converting enzyme in cytokine-mediated inducible nitric oxide synthase gene expression: Implications for neuroinflammatory diseases

Cited by 16 publications

References 38 publications

Cytokine profile in Leishmania-positive blood donors

Cytokine profile in Leishmania-positive blood donors

Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice

A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes

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