A novel mechanism for inhibition of lipopolysaccharide-induced proinflammatory cytokine production by valproic acid

Ulziisaikhan Jambalganiin, Bilegtsaikhan Tsolmongyn, Naoki Koide, Erdenezaya Odkhuu, Yoshikazu Naiki, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The inhibitory effect of valproic acid (VPA) on lipopolysaccharide (LPS)-induced inflammatory response was studied by using mouse RAW 264.7 macrophage-like cells. VPA pretreatment attenuated LPS-induced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, but not nuclear factor (NF)-κB and mitogen-activated protein kinases. VPA reduced phosphorylation of MDM2, an ubiquitin ligase and then prevented LPS-induced p53 degradation, followed by enhanced p53 expression. Moreover, p53 small interfering RNA (siRNA) abolished the inhibitory action of VPA on LPS-induced NF-κB p65 transcriptional activation and further LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. VPA prevented LPS-induced degradation of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and up-regulated the PTEN expression. Taken together, VPA was suggested to down-regulate LPS-induced NF-κB-dependent transcriptional activity via impaired PI3K/Akt/MDM2 activation and enhanced p53 expression. A detailed mechanism for inhibition of LPS-induced inflammatory response by VPA is discussed.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalInternational Immunopharmacology
Volume20
Issue number1
DOIs
Publication statusPublished - 05-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Fingerprint

Dive into the research topics of 'A novel mechanism for inhibition of lipopolysaccharide-induced proinflammatory cytokine production by valproic acid'. Together they form a unique fingerprint.

Cite this