TY - JOUR
T1 - A novel mechanism for inhibition of lipopolysaccharide-induced proinflammatory cytokine production by valproic acid
AU - Jambalganiin, Ulziisaikhan
AU - Tsolmongyn, Bilegtsaikhan
AU - Koide, Naoki
AU - Odkhuu, Erdenezaya
AU - Naiki, Yoshikazu
AU - Komatsu, Takayuki
AU - Yoshida, Tomoaki
AU - Yokochi, Takashi
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan ( 25460551 ) and a grant of MEXT -supported Program for the Strategic Research Foundation at Private Universities, 2011–2015 ( S1101027 ). We are grateful to K. Takahashi for the technical assistance.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84896451153
UR - https://www.scopus.com/pages/publications/84896451153#tab=citedBy
U2 - 10.1016/j.intimp.2014.02.032
DO - 10.1016/j.intimp.2014.02.032
M3 - Article
C2 - 24631367
AN - SCOPUS:84896451153
SN - 1567-5769
VL - 20
SP - 181
EP - 187
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 1
ER -