A Novel and Selective p38 Mitogen-Activated Protein Kinase Inhibitor Attenuates LPS-Induced Neuroinflammation in BV2 Microglia and a Mouse Model

Min Sung Gee, Sang Won Kim, Namkwon Kim, Soo Jin Lee, Myung Sook Oh, Hee Kyung Jin, Jae sung Bae, Kyung Soo Inn, Nam Jung Kim, Jong Kil Lee

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Neuroinflammation is an important pathological feature in neurodegenerative diseases. Accumulating evidence has suggested that neuroinflammation is mainly aggravated by activated microglia, which are macrophage like cells in the central nervous system. Therefore, the inhibition of microglial activation may be considered for treating neuroinflammatory diseases. p38 mitogen-activated protein kinase (MAPK) has been identified as a crucial enzyme with inflammatory roles in several immune cells, and its activation also relates to neuroinflammation. Considering the proinflammatory roles of p38 MAPK, its inhibitors can be potential therapeutic agents for neurodegenerative diseases relating to neuroinflammation initiated by microglia activation. This study was designed to evaluate whether NJK14047, a recently identified novel and selective p38 MAPK inhibitor, could modulate microglia-mediated neuroinflammation by utilizing lipopolysaccharide (LPS)-stimulated BV2 cells and an LPS-injected mice model. Our results showed that NJK14047 markedly reduced the production of nitric oxide and prostaglandin E2 by downregulating the expression of various proinflammatory mediators such as nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α and interleukin-1β in LPS-induced BV2 microglia. Moreover, NJK14047 significantly reduced microglial activation in the brains of LPS-injected mice. Overall, these results suggest that NJK14047 significantly reduces neuroinflammation in cellular/vivo model and would be a therapeutic candidate for various neuroinflammatory diseases.

Original languageEnglish
Pages (from-to)2362-2371
Number of pages10
JournalNeurochemical Research
Volume43
Issue number12
DOIs
StatePublished - 1 Dec 2018

Keywords

  • Kinase inhibitor
  • Lipopolysaccharide
  • Microglia
  • Neuroinflammation
  • P38 mitogen-activated protein kinase

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