Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

Abstract

Aim: Daidzein (4′,7-dihydroxyisoflavone) is an isoflavone exiting in many herbs that has shown anti-inflammation activity. The aim of this study was to investigate the mechanism underlying its anti-inflammatory action in murine lung epithelial cells. Methods: C57BL/6 mice were intranasally exposed to TNF-α to induce lung inflammation. The mice were injected with daidzein (400 mg/kg, ip) before TNF-α challenge, and sacrificed 12 h after TNF-α challenge, and lung tissues were collected for analyisis. In in vitro studies, murine MLE-12 epithelial cells were treated with TNF-α (20 ng/mL). The expression of pro-inflammatory chemokine Cxcl2 mRNA and NF-κB transcriptional activity were examined using real-time PCR and a dual reporter assay. Protein poly-adenosine diphosphate-ribosylation (PARylation) was detecyed using Western blotting and immunoprecipitation assays. Results: Pretreatment of the mice with daidzein markedly attenuated TNF-α-induced lung inflammation, and inhibited Cxcl2 expression in lung tissues. Furthermore, daidzein (10 μmol/L) prevented TNF-α-induced increases in Cxcl2 expression and activity and NF-κB transcriptional activity, and markedly inhibited TNF-α-induced protein PARylation in MLE-12 cells in vitro. In MLE-12 cells co-transfected with the PARP-1 expression plasmid and NF-κB-luc (or Cxcl2-luc) reporter plasmid, TNF-α markedly increased NF-κB (or Cxcl2) activation, which were significantly attenuated in the presence of daidzein (or the protein PARylation inhibitor PJ 34). PARP-1 activity assay showed that daidzein (10 μmol/L) reduced the activity of PARP-1 by ~75%. Conclusion: The anti-inflammatory action of daidzein in murine lung epithelial cells seems to be mediated via a direct interaction with PARP-1, which inhibits RelA/p65 protein PARylation required for the transcriptional modulation of pro-inflammatory chemokines such as Cxcl2.

Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes

“…The anti‐inflammatory effect of daidzein has also been examined by using TNFα‐treated (20 ng/mL) murine MLE‐12 epithelial cells. It was observed that daidzein treatment (10 μM) blocked the transcriptional activation of pro‐inflammatory genes and decreased the mRNA level of Cxcl2 in TNFα‐treated cells . Table represents the cell culture studies about the effect of daidzein or equol supplementation on glucose and lipid metabolism and vascular inflammation associated with T2D pathophysiology.…”

“…Many studies have reported the enhanced expression of several pro‐inflammatory cytokines including TNF‐α, IL‐1, IL‐6, and monocytec chemoattractant protein‐1 (MCP‐1) in the context of insulin resistance, obesity, T2Ds, and cardiovascular diseases . Daidzein treatment has been shown to suppress the activation of several inflammatory mediators associated with above‐mentioned diseases . Using adipocyte cell culture model, Sakamoto et al .…”

“…Moreover, daidzein supplementation in adipocyte and macrophage co‐culture system downregulated the gene expression of pro‐inflammatory cytokines and upregulated adiponectin gene expression by increasing PPARγ transcriptional activity. Anti‐inflammatory activity of daidzein has also been examined by using TNFα‐treated murine MLE‐12 epithelial cells . Results showed that daidzein treatment significantly inhibited the TNFα‐induced increase in Cxcl2 expression and activity and nuclear factor kappa‐B (NF‐κB) transcriptional activity and prevented the TNF‐α‐induced protein PARylation.…”

Protective effect of daidzein against streptozotocin‐induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model

“…In addition to this, daidzein is also used in treating cerebral ischemia because of its neuroprotective potential against oxygen‐glucose deficiency‐induced neurotoxicity and glutamate‐induced excitotoxicity in neural cells . Furthermore, daidzein has shown an anti‐inflammatory and neuroprotective effect upon oxidative stress‐induced Parkinson's disease in animal model . These findings proposed that daidzein might have a protective role in neurodegenerative disorder treatment associated with oxidative stress observed in case of AD.…”

c-Abl–Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes

“…In recent years, roles of PARP1 activation have been well acknowledged as to be involved in regulation of proinflammatory gene transcription in infectious and noninfectious as well as allergic disorders (12)(13)(14). Proinflammatory agents (e.g., LPS, IL-1, and TNF-a) that may not introduce severe damage to genomic DNA increase the level of protein PARylation in various cell types (15)(16)(17)(18). However, signaling mechanisms eliciting PARP1 activation remain poorly elucidated.…”