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Interleukin-1beta, inducible nitric oxide synthase, and nuclear factor-kappaB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-gamma injection.

Abstract

In a number of pathological states of the brain, the activation of the inducible nitric oxide synthase (iNOS) plays a major role. Interleukin (IL)-1beta is believed to be an essential factor in the induction of iNOS. However, little is known about the cascade of events culminating in iNOS expression in vivo. To identify the morphological as well as temporal relationship of lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) -induced microglial iNOS- and IL-1beta expression, a mixture of LPS and IFN-gamma was injected into the rat hippocampus. IL-1beta immunoreactivity was detected as early as 3 hr following surgery in ramified microglia in the lesioned hippocampus and in distal cortical layers adjacent to the pia mater. By 12 hr post-injection, IL-1beta immunoreactive, ramified microglia with swollen processes were widely distributed throughout hippocampal and neocortical areas, and staining was observed up to 48 hr after treatment. In contrast, iNOS immunostaining was seen in activated amoeboid microglia/macrophages in the ipsilateral hippocampus and around blood vessels but not earlier than 12 hr post-surgery. The temporal pattern of iNOS and IL-1beta expression corresponded to newly induced transcriptional activity as revealed by RT-PCR. Activation of NF-kappaB was restricted to brain regions in which IL-1beta was expressed and was detected both in microglia and astrocytes. A number of LPS/IFN-gamma-stimulated, IL-1beta-expressing microglia exhibited co-staining for activated NF-kappaB. The finding that IL-1beta precedes iNOS expression is consistant with a role of IL-1beta in the intercellular signaling events leading to microglial iNOS-induction. Co-localization of IL-1beta and NF-kappaB suggests an association between IL-1beta and NF-kappaB induction.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Leipzig, Germany.

    ,

    Source

    Journal of neuroscience research 57:3 1999 Aug 01 pg 388-98

    MeSH

    Animals
    Astrocytes
    Enzyme Induction
    Hippocampus
    Immunohistochemistry
    Injections
    Interferon-gamma
    Interleukin-1
    Lipopolysaccharides
    Male
    Microglia
    NF-kappa B
    Nitric Oxide Synthase
    Nitric Oxide Synthase Type II
    Rats
    Rats, Wistar
    Reverse Transcriptase Polymerase Chain Reaction

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    10412030

    Citation

    Hartlage-Rübsamen, M, et al. "Interleukin-1beta, Inducible Nitric Oxide Synthase, and Nuclear factor-kappaB Are Induced in Morphologically Distinct Microglia After Rat Hippocampal Lipopolysaccharide/interferon-gamma Injection." Journal of Neuroscience Research, vol. 57, no. 3, 1999, pp. 388-98.
    Hartlage-Rübsamen M, Lemke R, Schliebs R. Interleukin-1beta, inducible nitric oxide synthase, and nuclear factor-kappaB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-gamma injection. J Neurosci Res. 1999;57(3):388-98.
    Hartlage-Rübsamen, M., Lemke, R., & Schliebs, R. (1999). Interleukin-1beta, inducible nitric oxide synthase, and nuclear factor-kappaB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-gamma injection. Journal of Neuroscience Research, 57(3), pp. 388-98.
    Hartlage-Rübsamen M, Lemke R, Schliebs R. Interleukin-1beta, Inducible Nitric Oxide Synthase, and Nuclear factor-kappaB Are Induced in Morphologically Distinct Microglia After Rat Hippocampal Lipopolysaccharide/interferon-gamma Injection. J Neurosci Res. 1999 Aug 1;57(3):388-98. PubMed PMID: 10412030.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Interleukin-1beta, inducible nitric oxide synthase, and nuclear factor-kappaB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-gamma injection. AU - Hartlage-Rübsamen,M, AU - Lemke,R, AU - Schliebs,R, PY - 1999/7/21/pubmed PY - 1999/7/21/medline PY - 1999/7/21/entrez SP - 388 EP - 98 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 57 IS - 3 N2 - In a number of pathological states of the brain, the activation of the inducible nitric oxide synthase (iNOS) plays a major role. Interleukin (IL)-1beta is believed to be an essential factor in the induction of iNOS. However, little is known about the cascade of events culminating in iNOS expression in vivo. To identify the morphological as well as temporal relationship of lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) -induced microglial iNOS- and IL-1beta expression, a mixture of LPS and IFN-gamma was injected into the rat hippocampus. IL-1beta immunoreactivity was detected as early as 3 hr following surgery in ramified microglia in the lesioned hippocampus and in distal cortical layers adjacent to the pia mater. By 12 hr post-injection, IL-1beta immunoreactive, ramified microglia with swollen processes were widely distributed throughout hippocampal and neocortical areas, and staining was observed up to 48 hr after treatment. In contrast, iNOS immunostaining was seen in activated amoeboid microglia/macrophages in the ipsilateral hippocampus and around blood vessels but not earlier than 12 hr post-surgery. The temporal pattern of iNOS and IL-1beta expression corresponded to newly induced transcriptional activity as revealed by RT-PCR. Activation of NF-kappaB was restricted to brain regions in which IL-1beta was expressed and was detected both in microglia and astrocytes. A number of LPS/IFN-gamma-stimulated, IL-1beta-expressing microglia exhibited co-staining for activated NF-kappaB. The finding that IL-1beta precedes iNOS expression is consistant with a role of IL-1beta in the intercellular signaling events leading to microglial iNOS-induction. Co-localization of IL-1beta and NF-kappaB suggests an association between IL-1beta and NF-kappaB induction. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/10412030/Interleukin_1beta_inducible_nitric_oxide_synthase_and_nuclear_factor_kappaB_are_induced_in_morphologically_distinct_microglia_after_rat_hippocampal_lipopolysaccharide/interferon_gamma_injection_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0360-4012&date=1999&volume=57&issue=3&spage=388 DB - PRIME DP - Unbound Medicine ER -