Inhibition of histone deacetylases is the major pathway mediated by astaxanthin to antagonize LPS‐induced inflammatory responses in mammary epithelial cells

Abstract

Mastitis is a major inflammatory response of the mammary gland due to various pathogenic invasions and is a serious disease that affects the production yield and health status of cows. Astaxanthin (AST), a xanthophyll carotenoid, is a secondary metabolite synthesized by microalgae and yeasts that has been reported to suppress various inflammatory responses. However, the protective effect of AST on lipopolysaccharide (LPS)‐induced mammary epithelial cells has not yet been reported. The present study results indicated that AST treatment markedly attenuated the oxidative stress markers and nitric oxide (NO) while improving the anti‐oxidant enzymes in LPS exposed cells. On the other hand, LPS‐exposed cells showed nuclear translocation of nuclear factor‐κB (NF‐κB) with the activation of inflammatory cytokines such as monocyte chemoattractant protein‐1, tumor necrosis factor‐α, interferon‐γ, and interleukin‐6 (IL‐6). In addition, mRNA expression analysis revealed that the histone deacetylase (HDAC) ‐1, ‐2, ‐3, ‐6, ‐7 and pentraxin 3 (PTX3) expressions were increased in the LPS group. Furthermore, the activity of HDAC was increased to 2‐fold with a significant reduction in the histone acetyltransferase activity in cells exposed to LPS. However, AST was able to inhibit the nuclear translocation of NF‐κB with attenuated HDAC activity. Intriguingly, HDAC inhibition studies demonstrated that the cytokines such as IL‐4, IL‐8, granulocyte‐mcrophage colony stimulating factor, C‐reactive protein, IL‐17A, and IL‐22 were significantly suppressed which were upregulated in LPS treatment; while AST was found acting by improving the anti‐inflammatory cytokine IL‐10, and thioredoxin reductase levels. Collectively, these findings provide novel insights into the role of HDACs in regulating cellular processes involved in the pathogenesis of LPS‐induced mastitis as well as the potential use of AST as a therapeutic in treatment for controlling disease progression.

NF-κB–Dependent Snail Expression Promotes Epithelial–Mesenchymal Transition in Mastitis

“…This result is related to the levels of inflammatory factors secreted by the mammary epithelial cells. According to previous reports, the secretion levels of TNF-α and IL-6 in mammary epithelial cells are significantly lower than in alveolar epithelial cells after treatment with the same concentration of LPS [ 27 , 28 , 29 ]. In addition to the changes in cell morphology, our data showed that LPS increased the expression of Snail.…”

Network Pharmacology and Molecular Docking Approaches of Astaxanthin (ATX) against Atherosclerosis

“…By increasing IKBα levels through KLF5 and suppressing NF-kB, blocking miR-410 promotes the production of HDAC1 and delays the onset of atherosclerosis. [33] According to Venkidasamy and his team, [34] ATX successfully inhibited the upregulation of HDAC1 expression induced by Lipopolysaccharide (LPS) in mammary epithelial cells. This data may provide evidence that ATX could (ii) RXRA (PDB ID: 6JNO).…”

Protective Effect of Clostridium butyricum on Escherichia coli-Induced Endometritis in Mice via Ameliorating Endometrial Barrier and Inhibiting Inflammatory Response

“…There have been few reports about augmented HDAC activity in endometritis. HDACs are related to the removal of epsilon amino groups from the lysine residue in histones, causing the agglomeration of DNA chromatin ( 50 ). Previous studies have demonstrated that inhibition of HDAC increases histone acetylation, leading to a more open structure of chromatin and promoting DNA transcription ( 51 , 52 ).…”