Interleukin-1β, inducible nitric oxide synthase, and nuclear factor-κB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-γ injection
✍ Scribed by Maike Hartlage-Rübsamen; Rainer Lemke; Reinhard Schliebs
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 733 KB
- Volume
- 57
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
In a number of pathological states of the brain, the activation of the inducible nitric oxide synthase (iNOS) plays a major role. Interleukin (IL)-1 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-␥ (IFN-␥) -induced microglial iNOS-and IL-1 expression, a mixture of LPS and IFN-␥ was injected into the rat hippocampus. IL-1 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 postinjection, IL-1 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-1 expression corresponded to newly induced transcriptional activity as revealed by RT-PCR. Activation of NF-B was restricted to brain regions in which IL-1 was expressed and was detected both in microglia and astrocytes. A number of LPS/IFN-␥-stimulated, IL-1-expressing microglia exhibited co-staining for activated NF-B. The finding that IL-1 precedes iNOS expression is consistant with a role of IL-1 in the intercellular signaling events leading to microglial iNOS-induction. Colocalization of IL-1 and NF-B suggests an association between IL-1 and NF-B induction.