論文

査読有り
2017年1月

Apomorphine prevents LPS-induced IL-23 p19 mRNA expression via inhibition of JNK and ATF4 in HAPI cells

EUROPEAN JOURNAL OF PHARMACOLOGY
  • Hirokazu Hara
  • ,
  • Dai Kimoto
  • ,
  • Miho Kajita
  • ,
  • Chisato Takada
  • ,
  • Tetsuro Kamiya
  • ,
  • Tetsuo Adachi

795
開始ページ
108
終了ページ
114
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ejphar.2016.12.014
出版者・発行元
ELSEVIER SCIENCE BV

Inflammation has been reported to be closely related to exaggeration of cerebral ischemia and neurodegenerative diseases. Microglia, resident immune cells in the central nervous system, can be activated in response to neuronal injury and produce proinflammatory cytokines, resulting in further aggravation of neuronal injury. Interleukin (IL)-23, which consists of p19 and IL-12 p40 subunits, has been shown to be involved in brain injury associated with neuroinflammation. Apomorphine (Apo), a nonselective dopamine receptor agonist, has been used for clinical therapy of Parkinson's disease. Besides the pharmacological effect, Apo is known to have pleiotropic biological functions. In this study, to elucidate the effect of Apo on lipopolysaccharide (LPS)-induced IL-23 p19 mRNA expression in microglial cell line HAPI cells, we pretreated cells with various concentrations of Apo (10 30 mu M) for 8, 16, and 24 h, followed by exposure to LPS (100 ng/ml). Pretreatment with Apo dose and time-dependently suppressed the induction of IL-23 p19 mRNA. However, this effect of Apo was exerted independently of dopamine receptors. JNK and ATF4, an endoplasmic reticulum (ER) stress-inducible transcription factor, were involved in expression of LPS-induced IL-23 p19 mRNA. Pretreatment with Apo (30 mu M) for 24 h inhibited LPS-induced activation of JNK and the nuclear accumulation of ATF4. Thapsigargin (Tg), an ER stress inducer, stimulated IL-23 p19 mRNA expression via an ATF4 dependent mechanism. We also found that Apo inhibited Tg-induced ATF4 accumulation and IL-23 p19 mRNA expression. Taken together, our findings suggest that Apo exerts anti-inflammatory effects through inhibition of JNK and ATF4 signaling pathways.

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1016/j.ejphar.2016.12.014
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27939990
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000393542800015&DestApp=WOS_CPL