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Leptomycin B, a metabolite of Streptomyces, inhibits the expression of inducible nitric oxide synthase in BV2 microglial cells

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Affiliated Author(s)
장병철박종구박종욱서민호서성일
Alternative Author(s)
Jang, Byeong ChurlPark, Jong GuPark, Jong WookSuh, Min HoSuh, Seong Il
Journal Title
International Journal of Oncology
ISSN
1019-6439
Issued Date
2006
Abstract
. Overexpression of inducible nitric oxide synthase
(iNOS) and the resultant overproduction of NO has been
implicated in neuronal inflammatory diseases. Leptomycin B
(LMB), a metabolite of Streptomyces, has been identified as a
specific inhibitor of CRM1 nuclear export receptor. In this
study, we evaluated the effect of LMB on lipopolysaccharide
(LPS)-induced iNOS expression in BV2 cells, a murine
microglial cells and the associated mechanisms. LMB
strongly inhibited LPS-induced iNOS protein and mRNA
expressions in BV2 cells in which 10 ng/ml of LMB (18 nM)
was sufficient to greatly down-regulate iNOS by LPS,
suggesting the potency of LMB to inhibit iNOS. The data of
iNOS promoter-driven luciferase assay further suggested that
the LMB inhibitory effect was in part due to inhibition of
iNOS transcription. However, LPS-induced activation of
various intracellular signaling proteins, such as nuclear
factor-κB (NF-κB), extracellular signal-regulated kinases
(ERKs), p38s, and c-Jun N-terminal kinases (JNKs), whose
activations are known to be important for iNOS expression
by LPS in BV2 cells, were not affected in the presence of
LMB. Together, these results suggest that LMB inhibits iNOS
expression in response to LPS in BV2 microglia, and the
inhibition seems to be associated with blockage of CRM1-
mediated iNOS mRNA nuclear export and also in part
transcriptional down-regulation of iNOS, but not through
modulation of NF-κB and the mitogen-activated protein kinase
signaling pathways.
Department
Dept. of Molecular Medicine (분자의학)
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Institute for Medical Science (의과학연구소)
Publisher
School of Medicine
Citation
BYEONG-CHURL JANG et al. (2006). Leptomycin B, a metabolite of Streptomyces,
inhibits the expression of inducible nitric
oxide synthase in BV2 microglial cells. International Journal of Oncology, 29(6), 1509–1515. doi: 10.3892/ijo.29.6.1509
Type
Article
ISSN
1019-6439
DOI
10.3892/ijo.29.6.1509
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35930
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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