The anti-inflammatory effects of
sodium valproate (VPA) in vivo and in vitro have been demonstrated in recent studies. The aim of this study was to evaluate whether VPA can suppress
inflammation in bovine mammary epithelial cells (BMECs) stimulated by γ-D-glutamyl-meso-
diaminopimelic acid (
iE-DAP). First, the concentration and treatment points of
iE-DAP and VPA were optimized. Then, BMECs were cultured in complete media and separated into four groups: untreated control cells (CON group), cells stimulated by 10 μg/mL
iE-DAP for 6 h (DAP group), cells stimulated by 0.5 mmol/L VPA for 6 h (VPA group), and cells pretreated with VPA (0.5 mmol/L) for 6 h followed by 10 μg/mL of
iE-DAP for 6 h (VD group). The results showed that the level of interleukin-6 (IL-6) and
tumor necrosis factor-α (TNF-α) in the culture medium increased in the
iE-DAP-treated cells and that pretreatment with VPA reversed this increase.
iE-DAP increased both
mRNA and
protein expression levels of
nucleotide-binding oligomerization domain-containing
protein 1 (NOD1) and receptor-interacting
protein kinas (RIPK2) and activated inhibitor of NF-κB (IκB) and
nuclear factor-kappa B p65 (NF-κB p65) through phosphorylation. Upon activation of the NF-κB pathway, the expression of the pro-inflammatory
cytokines IL-6,
interleukin-8 (IL-8) and interleukin-1β (IL-1β), the
acute phase protein serum amyloid A 3 (SAA3) and the
lingual antimicrobial peptide (LAP) but not haptoglobi (HP) or bovine neutrophil beta defensing 5 (BNBD5) were increased in the DAP group. The VPA pretreatment induced the acetylation of signal transducers and activators of transcription(STAT1) and
histone 3 (H3) by inhibiting
histone deacetylase (HDAC) and then suppressed the NF-κB pathway. Moreover, VPA induced autophagy and reduced apoptosis in BMECs in the VD group. These results suggested that VPA treatment can attenuate the inflammatory response induced by
iE-DAP.