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Anti-inflammatory effects of N-cyclooctyl-5-methylthiazol-2-amine hydrobromide on lipopolysaccharide-induced inflammatory response through attenuation of NLRP3 activation in microglial cells

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Abstract
Microglial activation is closely associated with neuroinflammatory pathologies. The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasomes are highly organized intracellular sensors of neuronal alarm signaling. NLRP3 inflammasomes activate nuclear factor kappa-B (NF-kappa B) and reactive oxygen species (ROS), which induce inflammatory responses. Moreover, NLRP3 dysfunction is a common feature of chronic inflammatory diseases. The present study investigated the effect of a novel thiazol derivative, N-cyclooctyl-5-methylthiazol-2-amine hydrobromide (KHG26700), on inflammatory responses in lipopolysaccharide (LPS)-treated BV-2 microglial cells. KHG26700 significantly attenuated the expression of several pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, in these cells, as well as the LPS-induced increases in NLRP3, NF-kappa B, and phospho-IkB alpha levels. KHG26700 also suppressed the LPS-induced increases in protein levels of autophagy protein 5 (ATG5), micro-tubule-associated protein 1 light chain 3 (LC3), and beclin-1, as well as downregulating the LPS-enhanced levels of ROS, lipid peroxidation, and nitric oxide. These results suggest that the anti-inflammatory effects of KHG26700 may be due, at least in part, to the regulation of the NLRP3-mediated signaling pathway during microglial activation.
Author(s)
김은아황교욱김지은안지인최수영양승주조성우
Issued Date
2021
Type
Article
Keyword
InflammasomeMicrogliaN-cycooctyl-5-methylthiazol-2-amine hydrobromideNLRP3pro-inflammatory cytokines
DOI
10.5483/BMBRep.2021.54.11.082
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8302
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_kiss_primary_3916454&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Anti-inflammatory%20effects%20of%20N-cyclooctyl-5-methylthiazol-2-amine%20hydrobromide%20on%20lipopolysaccharide-induced%20inflammatory%20response%20through%20attenuation%20of%20NLRP3%20activation%20in%20microglial%20cells&offset=0&pcAvailability=true
Publisher
BMB REPORTS
Location
대한민국
Language
영어
ISSN
1976-6696
Citation Volume
54
Citation Number
11
Citation Start Page
557
Citation End Page
562
Appears in Collections:
Medicine > Medicine
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