Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway.

The purpose of this study was to investigate the protective effect of PD against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its potential mechanism. In vivo, PD and dexamethasone were intraperitoneally administered 1h before LPS stimulation. Then, mice were sacrificed at 6h post-LPS stimulation. Neutrophil number, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were determined, as well as lung wet to dry ratio (W/D) and polymorphonuclear (MPO) activity. The protein expressions of Toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), IL-1R-associated kinases 1 (IRAK1), IRAK4, inhibitor of nuclear factor kappa-B kinase (IKK)α, p-IKKα, IKKβ, p-IKKβ, inhibitor of NF-κB (IκBα), p-IκBα and NF-κB in lung tissues were assessed. Besides, we detected the IL-6, IL-1β, IL-8, TNF-α levels and TLR4, MyD88, NF-κB protein expressions in LPS-induced BEAS-2B cells. Consequently, PD significantly inhibited the levels of W/D, MPO, neutrophils number, TNF-α, IL-6, IL-1β and reversed TLR4-MyD88-NF-κB signaling pathway in lung tissues. In vitro assays, PD effectively negatively mediated the inflammatory cytokines and ameliorated the high expressions of TLR4, MyD88, NF-κB caused by LPS simulation in Human bronchial epithelial BEAS-2B cells. This study indicated that PD played a protective role in LPS-induced ALI and BEAS-2B cells. The results supported further study of PD as potential candidate for acute lung injury.

Jiang Q ，Yi M ，Guo Q ，Wang C ，Wang H ，Meng S ，Liu C ，Fu Y ，Ji H ，Chen T ... -  《-》

The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways.

The aim of present study was to evaluate the protective effects of dexmedetomidine (DEX) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and investigate its possible mechanisms mediated by HMGB1. In vivo, pulmonary pathology observation and myeloperoxidase (MPO) activity were also examined to evaluate the protective effect of DEX in the lungs. Tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), serum and lung tissues LPS-induced rats were detected. The oxidative indices including superoxide dismutase (SOD), Malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum were also determined. Additionally, nitric oxide (NO), TNF-α, IL-6 and IL-1β, MDA, SOD and GSH-Px in the supernatants of LPS-induced BEAS-2B cells were measured. Furthermore, we detected the protein expression of high mobility group box-1 protein (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), inhibitor of NF-κB (IκBα), p-IκBα, nuclear factor kappa-B (NF-κB), p-NF-κB, phosphatidylinositol 3'-kinase (PI3K), p-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR) and p-mTOR in LPS-induced ALI rats and LPS-induced BEAS-2B cells. Immunohistochemical and immunofluorescence analyses of HMGB1 in lung tissues or BEAS-2B cells were also conducted to evaluate the mechanisms of DEX. DEX effectively attenuated pulmonary pathology, and ameliorated the levels of MPO, SOD, MDA, GSH-Px, TNF-α, IL-6, IL-1β and NO in LPS-stimulated rats and BEAS-2B cells. Additionally, treatment with DEX inhibited the expression of HMGB1, TLR4, MyD88, p-IκB, p-NF-κB, p-PI3K, p-Akt and p-mTOR in vivo and in vitro. Immunohistochemical and immunofluorescence analyses also showed that DEX suppressed HMGB1 levels in lung sections and BEAS-2B cells. Treatment with glycyrrhizin, an inhibitor of HMGB1, confirmed that HMGB1 was involved in the mechanism of DEX on LPS-induced ALI. The transfection of HGMB1 siRNA also confirmed these findings in vitro. In conclusion, the present study showed that DEX exerted a protective effect on LPS-induced ALI rats likely through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways.

Meng L ，Li L ，Lu S ，Li K ，Su Z ，Wang Y ，Fan X ，Li X ，Zhao G ... -  《-》

Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro.

The purpose of the present study was to investigate the protective role of acteoside (AC) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). BalB/c mice intraperitoneally received AC (30, and 60 mg/kg) or dexamethasone (2 mg/kg) 2h prior to or after intratracheal instillation of LPS. Treatment with AC significantly decreased lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity and ameliorated LPS-induced lung histopathological changes. In addition, AC increased super oxide dismutase (SOD) level and inhibited malondialdehyde (MDA) content, total cell and neutrophil infiltrations, and levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) in LPS-stimulated mice. Furthermore, we demonstrated that AC inhibited the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, inhibitor of nuclear factor kappa-B kinase-α (IKK-α) and inhibitor of nuclear factor kappa-B kinase-β (IKKβ) in LPS-induced inflammation in A549 cells. Our data suggested that LPS evoked the inflammatory response in lung epithelial cells A549. The experimental results indicated that the protective mechanism of AC might be attributed partly to the inhibition of proinflammatory cytokine production and NF-κB activation.

Jing W ，Chunhua M ，Shumin W 《-》

Kegan Liyan oral liquid ameliorates lipopolysaccharide-induced acute lung injury through inhibition of TLR4-mediated NF-κB signaling pathway and MMP-9 expression.

Kegan Liyan oral liquid (KGLY), a Chinese prescription modified from classic formulas Yin-Qiao-San (from TCM classic Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian), has been reported to exert heat-clearing and detoxifying effects and used extensively for the treatment of severe pulmonary diseases in clinics including influenza, cough and pneumonia. The purpose of this study was to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. Mice were orally administrated with KGLY (50, 100 and 150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung wet/dry (W/D) weight ratio, histopathological examinations and biochemical analyses. The cell counts, protein concentration, interleukin-1β (IL-1β), interleukin-6 (IL-6), necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile, the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), as well as matrix metalloproteinases 9 (MMP-9) were determined by western blot assay. KGLY significantly prolonged mice survival time and ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated LPS-induced acute pulmonary inflammation via decreasing the expressions of cytokines and chemokines (IL-1β, IL-6, TNF-α, and MIP-2), enhanced the activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of MPO and MDA, and down-regulated the expressions of TLR4, NF-κB and MMP9. The results suggested that the relieving effect of KGLY against LPS-induced ALI might be partially due to suppression of oxidative stress and inflammatory response, inhibition of TLR4-mediated NF-κB activation, and down-regulation of MMP9 expression, indicating it may be a potential therapeutic agent for ALI.

Zhang X ，Sun CY ，Zhang YB ，Guo HZ ，Feng XX ，Peng SZ ，Yuan J ，Zheng RB ，Chen WP ，Su ZR ，Huang XD ... -  《-》

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway.

Ju M ，Liu B ，He H ，Gu Z ，Liu Y ，Su Y ，Zhu D ，Cang J ，Luo Z ... -  《-》