Role of the Rho/ROCK signaling pathway in the protective effects of fasudil against acute lung injury in septic rats

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

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NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

Mediators of Inflammation ◽

10.1155/2016/7349603 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Jianhua Huang ◽

Li Li ◽

Weifeng Yuan ◽

Linxin Zheng ◽

Zhenhui Guo ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Binding Domain ◽

Dependent Manner ◽

Protective Effects ◽

Lps Challenge ◽

Domain Peptide ◽

Nemo Binding Domain ◽

Dose Dependent

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-αand NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-αand IL-1βsecretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

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The Role of p38 MAPK Signaling Pathway in Macrophage Pyroptosis and Murine Acute Lung Injury

Immunome Research ◽

10.4172/1745-7580.1000142 ◽

2017 ◽

Vol 13 (3) ◽

Author(s):

Dandan Li ◽

Wei Ying Ren ◽

Zhilong Jiang ◽

Lei Zhu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

P38 Mapk ◽

Mapk Signaling ◽

Mapk Signaling Pathway

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Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.746964 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu-Qiong He ◽

Can-Can Zhou ◽

Jiu-Ling Deng ◽

Liang Wang ◽

Wan-Sheng Chen

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Inflammatory Responses ◽

Lung Edema ◽

Protective Effects ◽

And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

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Emodin Attenuates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis Signaling Pathway In vitro and In vivo

Inflammation ◽

10.1007/s10753-021-01581-1 ◽

2021 ◽

Author(s):

Yuhan Liu ◽

Luorui Shang ◽

Jiabin Zhou ◽

Guangtao Pan ◽

Fangyuan Zhou ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Nlrp3 Inflammasome ◽

Quantitative Polymerase Chain Reaction ◽

Interleukin 1 ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects

Abstract—Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1β) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1β, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.

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The Role of Vagus Nerve on Dexmedetomidine Induced Survival and Lung Protection in a Sepsis Model in Rats.

10.21203/rs.3.rs-483367/v1 ◽

2021 ◽

Author(s):

Yumo Li ◽

Binbin Wu ◽

Cong Hu ◽

Jie Hu ◽

Qingquan Lian ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Vagus Nerve ◽

Vagal Nerve ◽

Lung Injury Score ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Lung Protection ◽

Tnf Α

Abstract BackgroundSepsis often results in acute lung injury (ALI). Sedative dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in a model of lipopolysaccharide (LPS)-induced ALI in rats. MethodsThe bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed without section as sham surgery. The ALI was induced by intraperitoneal injection of LPS (1 or 10 mg/kg). After LPS administration, Dex antagonist yohimbine (YOH) (1 mg/kg) and/or Dex (25 μg/kg) was injected intraperitoneally at 0, 4, 8 and 12 hours to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores of haematoxylin and eosin (H-E) staining sections. The plasma concentrations of interleukin 1beta (IL-1β), tumour necrosis factor-alpha (TNF-α), catecholamine (CA) and acetylcholine (Ach) were measured with enzyme-linked immunosorbent assay (ELISA). ResultsThe median survival time of LPS-induced ALI rats was significantly prolonged by Dex (22 hours, 50% CI, [31.25, 90.63]) compared that in the LPS group (14 hours, 50% CI, [18.75, 81.25], P < 0.05), and the acute lung injury score was significantly reduced by Dex (6.5, 50% CI, [5.75, 7.5] vs 11.5, 50% CI, [10.75, 12.50] in the LPS group, P < 0.01). However, these protective effects of Dex were significantly reduced by either YOH administration or vagotomy. Dex significantly decreased LPS-induced plasma IL-1β (pg/ml) (20.75 ± 0.78 vs. 30.22 ± 2.62, P < 0.01), TNF-α (pg/ml) (205.30 ± 9.39 vs. 273.40 ± 14.50, P < 0.01), and CA (pg/ml) (825.70 ± 43.46 vs. 1188.00 ± 64.40, P < 0.01) but increased the secretion of Ach (pg/ml) (507.20 ± 49.52 vs. 296.50 ± 62.44, P < 0.01); these effects of Dex was partially abolished by vagotomy. ConclusionsOur data suggested that Dex increased vagal nerve tone which partially contributed to its anti-inflammatory and lung protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and α 2 -adrenoceptor activation, respectively.

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