Sodium butyrate suppresses NOD1‐mediated inflammatory molecules expressed in bovine hepatocytes during iE‐DAP and LPS treatment

Abstract

Nucleotide oligomerization domain protein-1 (NOD1), a cytosolic pattern recognition receptor for the γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) is associated with the inflammatory diseases. Very little is known how bovine hepatocytes respond to specific ligands of NOD1 and sodium butyrate (SB). Therefore, the aim of our study was to investigate the role of bovine hepatocytes in NOD1-mediated inflammation during iE-DAP or LPS treatment or SB pretreatment. To achieve this aim, hepatocytes separated from cows at ∼160 days in milk (DIM) were divided into six groups: The nontreated control group (CON), the iE-DAP-treated group (DAP), the lipopolysaccharide-treated group (LPS), iE-DAP with SB group (DSB), LPS with SB group (LSB), and the SB group. Both iE-DAP and LPS highly increased the expression of both NOD1 and RIPK2, the two key factors for the immune response in hepatocytes. IκBα, NF-κB/p65, and MAP kinases (ERK, JNK, and p38) were activated through phosphorylation. The activation of NF-κB and MAPK pathway consequently increased the proinflammatory cytokines, IL-6, TNF-α, IL-8, and IFN-γ and the chemokines CCL5, CCL20, and CXCL-10.Both treatments improved iNOS/NOS2 expression. However, iE-DAP was failed to express acute phase protein SAA3, but HP and LPS HP but SAA3. These ligands also increased LRRK2, TAK1, TAB1, and β-defensins expression. The SB pretreatment at lower dose restored the function of hepatocytes by suppressing these increased molecules, as HDAC3 was inhibited. The activated NOD1 negatively regulated the expression of FOXA2. Altogether these data suggest an important role of bovine hepatocytes to promote immune responses via NOD1 expression during infection in the liver and a key role of SB to attenuate inflammation.

Berberine Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis and Inhibits the Secretion of Gut Lysozyme via Promoting Autophagy

“…NOD1 is widely expressed in IECs and laminar immune cells, and its expression in macrophages and IECs is important for inducing the immune response to bacteria and the production of antimicrobial peptides [ 43 ]. NOD1 can also activate the NF-κB and MAPK pathways to regulate inflammation reaction [ 44 ]. We examined the pathway of ATG16L1/NOD1/RIPK2 in IEC-18 and found that BBR can increase the expression of ATG16L1 and reduce the expression of NOD1 and RIPK2 in both RNA and protein levels.…”

The RIPK family: expression profile and prognostic value in lung adenocarcinoma

“…RIPK2 is also known as RIP-like-interacting caspase-like apoptosis-regulatory protein kinase or CARD-containing IL-1b converting enzyme-associated kinase [ 1 , 23 ]. RIPK2, as a critical protein for the signaling from NOD-like receptors, always triggered MAPK, ERK2, and JNK activation and further affect apoptosis [ 24 ]. Thus, target treatment on RIPK2 showed an ideal control of inflammatory diseases, such as cystic fibrosis, asthma, inflammatory bowel disease and pancreatitis [ 3 , 25 , 26 ].…”

Sodium Butyrate More Effectively Mitigates the Negative Effects of High-Concentrate Diet in Dairy Cows than Sodium β-Hydroxybutyrate via Reducing Free Bacterial Cell Wall Components in Rumen Fluid and Plasma

“…Sodium butyrate could inhibit the inflammation induced by iE-DAP and LPS in bovine hepatocytes via suppressing NOD1and NOD1-mediated inflammatory molecules (IL6, IL8, TNF-α, etc.) expression in vitro [ 12 , 16 ]. Similarly, several studies have suggested that supplementation of sodium butyrate could comprehensively reduce the body injuries induced by HC diet in ruminants.…”

“…Sodium butyrate, as a histone deacetylase (HDAC) inhibitor, facilitates gene transcription by inhibiting HDAC [ 10 , 16 ] and possesses anti-inflammatory, anti-oxidative, anti-apoptotic and other activities [ 12 ]. In addition, oral administration of sodium butyrate promotes ruminal development and improves production performance and health status in young calves [ 10 , 17 ].…”