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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.
J Neurosci Res 1999; 57(3):388-98JN

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.

Authors+Show Affiliations

Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Leipzig, Germany.No affiliation info availableNo affiliation info available

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 -