↓ Skip to main content

Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes

Overview of attention for article published in Brain Research Protocols, January 2001
Altmetric Badge

Mentioned by

patent
1 patent

Citations

dimensions_citation
31 Dimensions

Readers on

mendeley
22 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes
Published in
Brain Research Protocols, January 2001
DOI 10.1016/s0006-8993(00)03181-4
Pubmed ID
Authors

Dj. Miljkovic, T. Samardzic, M. Mostarica Stojkovic, S. Stosic-Grujicic, D. Popadic, V. Trajkovic

Abstract

Highly reactive gaseous free radical nitric oxide (NO), generated by astrocytes and infiltrating macrophages is implicated in inflammatory destruction of brain tissue, including that occurring in multiple sclerosis. Therefore, the influence of immunosuppressive drug leflunomide on inducible nitric oxide synthase (iNOS)-dependent NO production in rat astrocytes and macrophages was investigated. Under the same cultivating conditions, leflunomide's active metabolite A77 1726 caused a dose-dependent decrease of NO production in IFN-gamma+LPS-stimulated primary astrocytes, but not in macrophages. While A77 1726 did not alter iNOS enzymatic activity, it markedly suppressed IFN-gamma+LPS-triggered expression of iNOS mRNA in astrocytes. In the presence of transcription inhibitor actinomycin D, A77 1726 failed to inhibit astrocyte NO production, suggesting transcriptional regulation of iNOS by leflunomide. This assumption was further supported by the ability of A77 1726 to inhibit IFN-gamma+LPS-induced expression of mRNA for an important iNOS transcription factor IRF-1. PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MAPKK/MEK), but not genistein, an unselective protein tyrosine kinase inhibitor, completely mimicked cell type-specific inhibition of NO synthesis by A77 1726. Therefore, previously described inhibition of MEK/MAP pathway by leflunomide could present a possible mechanism for A77 1726-mediated suppression of iNOS activation in astrocytes. Accordingly to results obtained with primary astrocytes, both A77 1726 and PD98059 significantly reduced IFN-gamma+LPS-induced NO synthesis in the cultures of rat astrocytoma cell line C6. The ability to suppress iNOS induction in astrocytes supports potential use of leflunomide in the treatment of multiple sclerosis and other NO-dependent inflammatory brain disorders.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 27%
Professor 4 18%
Student > Bachelor 3 14%
Professor > Associate Professor 3 14%
Student > Master 1 5%
Other 3 14%
Unknown 2 9%
Readers by discipline Count As %
Medicine and Dentistry 5 23%
Agricultural and Biological Sciences 4 18%
Immunology and Microbiology 3 14%
Neuroscience 2 9%
Biochemistry, Genetics and Molecular Biology 1 5%
Other 3 14%
Unknown 4 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 October 2002.
All research outputs
#8,676,672
of 25,714,183 outputs
Outputs from Brain Research Protocols
#3,111
of 10,830 outputs
Outputs of similar age
#26,526
of 115,234 outputs
Outputs of similar age from Brain Research Protocols
#39
of 100 outputs
Altmetric has tracked 25,714,183 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 10,830 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 115,234 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 100 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.