Lonicerin prevents inflammation and apoptosis in LPS-induced acute lung injury.

Acute lung injury (ALI) is a life-threatening condition caused by severe inflammation of lung tissues. We hypothesized that lipopolysaccharide induced acute lung inflammation and injury in mice might be controlled by lonicerin (LCR), a plant flavonoid that impacts immunity, oxidative stress, and cell proliferation. LCR reduced pathological changes including pulmonary edema, elevation of protein in bronchoalveolar lavage, inflammation, pro-inflammatory gene expression, expression of toll-like receptor 4/nuclear factor-kappa B, apoptosis, and significantly reduced mortality. Together, the results suggest that LCR might be a potential and effective candidate for the treatment of ALI that acts by inhibiting inflammation and apoptosis.

Histone deacetylases 3 deletion restrains PM2.5-induced mice lung injury by regulating NF-κB and TGF-ß/Smad2/3 signaling pathways.

Acute lung injury (ALI) as a serious disease with high mortality has been emphasized as a threat to human health and life. Accumulating studies demonstrated that PM2.5 plays a significant role in metabolic and lung diseases. Histone deacetylases 3 (HDAC3) is an important regulator in control of gene transcription, required in up-regulation of inflammation-related signaling, and has been known as a key hotpot in treating a lot of chronic inflammatory diseases. TGF-ß/Smad signaling pathway has been proven to be of significance in fibrosis development. Our results found that PM2.5 induced lung function injury in WT mice with a inflammatory responses through the activation of TGF-ß/Smad signaling pathways, resulting in lung injury. Of note, HDAC3-deficient mice after PM2.5 administration further promoted TGF-ß/Smad signaling pathways activation. In addition, TLR4, p-NF-κB and p-IκBα indicated that HDAC3 knockout mice have a higher inflammation-related signals expression in lung tissue than WT mice after PM2.5 administration, resulting in pro-inflammatory cytokines releasing. Moreover, in vitro experiment of lung epithelial cells challenged with PM2.5, further indicated that TGF-ß/Smad2/3 was involved in fibrosis development, leading to inflammation response. Also, the activation of TLR4/NF-κB could be observed in PM2.5-induced lung epithelial cells, leading to inflammation infiltration. These results indicate a new therapeutic target to protect against lung injury caused by PM2.5.

Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.