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A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia

Title
A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia
Authors
Kim W.-K.Jang P.-G.Woo M.-S.Han I.-O.Piao H.Z.Lee K.Lee H.Joh T.H.Kim H.-S.
Ewha Authors
김원기김희선
SCOPUS Author ID
김희선scopus
Issue Date
2004
Journal Title
Neuropharmacology
ISSN
0028-3908JCR Link
Citation
vol. 47, no. 2, pp. 243 - 252
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Excessive proinflammatory cytokine and NO production by activated microglia play a role in neurodegenerative disorders. In this study, we found that a new compound KL-1037 suppressed LPS-induced NO release/inducible nitric oxide synthase expression in BV2 mouse microglial cells. In addition, KL-1037 prominently diminished LPS-induced production of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, while it increased anti-inflammatory IL-10 and TGF-β1 production. By RNase protection assay and RT-PCR, we showed that KL-1037 regulated iNOS and cytokines at transcriptional or post-transcriptional level. Further analysis of molecular mechanisms revealed that KL-1037 prominently increased intracellular cAMP levels and potentiated LPS-induced pCREB expression. However, LPS-induced MAP kinase or NF-κB activities were slightly or little changed by KL-1037. Treatment with cAMP antagonist or IL-10 neutralizing antibody completely reversed upregulation of IL-10 and partially repression of TNF-α or NO induced by KL-1037. These data suggest that microglial inactivation by KL-1037 is at least in part due to activation of PKA pathway and/or upregulation of IL-10. Thus, repressing proinflammatory cytokines and iNOS gene expression in activated microglia by KL-1037 may provide potential therapeutic strategies for various neurodegenerative diseases including ischemic cerebral disease. © 2004 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.neuropharm.2004.03.019
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자연과학대학 > 화학·나노과학전공 > Journal papers
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