Novel Interventional Approaches for ALI/ARDS: Cell-Based Gene Therapy

Zhu, Yinggang; Jian, Qu; Zhang, Jin; Jiang, Huai; Xu, Jin‐Fu

doi:10.1155/2011/560194

Cited by 16 publications

(13 citation statements)

References 69 publications

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“…Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are well-known fatal diseases with an extremely high morbidity rate (35% to 50%) in critically ill patients [ 1 , 2 , 3 ]. According to reports, approximately 190,000 new cases were diagnosed in the United States per year [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 9 ]. The multiple etiologies, including severe sepsis, pneumonia, lung abscess and severe burn, cause uncontrolled and self-amplified pulmonary inflammation which lie at the center of the pathology of ALI/ARDS [ 2 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-κB in Mice

Xiao

Zhu

Zhang

et al. 2014

IJMS

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Acute lung injury (ALI) and its severe manifestation of acute respiratory distress syndrome (ARDS) are well-known illnesses. Uncontrolled and self-amplified pulmonary inflammation lies at the center of the pathology of this disease. Emodin, the bio-active coxund of herb Radix rhizoma Rhei, shows potent anti-inflammatory properties through inactivation of nuclear factor-κB (NF-κB). The aim of this study was to evaluate the effect of emodin on lipopolysaccharide (LPS)-induced ALI in mice, and its potential bio-mechanism. In our study, BALB/c mice were stimulated with LPS to induce ALI. After 72 h of LPS stimulation, pulmonary pathological changes, lung injury scores, pulmonary edema, myeloperoxidase (MPO) activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid (BALF), and MCP-1 and E-selectin expression were notably attenuated by emodin in mice. Meanwhile, our data also revealed that emodin significantly inhibited the LPS-enhanced the phosphorylation of NF-κB p65 and NF-κB p65 DNA binding activity in lung. Our data indicates that emodin potently inhibits OPEN ACCESS Int. J. Mol. Sci. 2014, 15 19356 LPS-induced pulmonary inflammation, pulmonary edema and MCP-1 and E-selectin expression, and that these effects were very likely mediated by inactivation of NF-κB in mice. These results suggest a therapeutic potential of emodin as an anti-inflammatory agent for ALI/ARDS treatment.

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Section: Introductionmentioning

confidence: 99%

Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-κB in Mice

Xiao

Zhu

Zhang

et al. 2014

IJMS

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“…More recently, human recombinant Ang-1, administered 8 hours before and in combination with LPS, also protected mice against pulmonary hyperpermeability in vivo through a p190 RhoGAP-dependent mechanism [11]. However, adenoviral delivery is not plausible in humans, while a large-scale production of recombinant Ang-1, which has a short half-life in vivo [12], is hindered by the aggregation and insolubility of this protein [13]. Moreover, septic patients need efficacious treatments after the disease has already developed [6].…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

et al. 2012

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IntroductionSevere sepsis is characterised by intravascular or extravascular infection with microbial agents, systemic inflammation and microcirculatory dysfunction, leading to tissue damage, organ failure and death. The growth factor angiopoietin (Ang-1) has therapeutic potential but recombinant Ang-1 tends to aggregate and has a short half-life in vivo. This study aimed to investigate the acute effects of the more stable Ang-1 variant matrilin-1-angiopoietin-1 (MAT.Ang-1) on the function of the microcirculation in an experimental model of sepsis, and whether any protection by MAT-Ang-1 was associated with modulation of inflammatory cytokines, angiogenic factors or the endothelial nitric oxide synthase (eNOS)-Akt and vascular endothelial (VE)-cadherin pathways.MethodsAluminium window chambers were implanted into the dorsal skinfold of male C3H/HeN mice (7 to 10 weeks old) to expose the striated muscle microcirculation. Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg at 0 and 19 hours). MAT.Ang-1 was administered intravenously 20 hours after the onset of sepsis. Microcirculatory function was evaluated by intravital microscopy and Doppler fluximetry.ResultsEndotoxemia resulted in macromolecular leak, which was ameliorated by MAT.Ang-1 post-treatment. LPS induced a dramatic reduction in tissue perfusion, which was improved by MAT.Ang-1. Proteome profiler array analysis of skeletal muscle also demonstrated increased inflammatory and reduced angiogenic factors during endotoxemia. MAT.Ang-1 post-treatment reduced the level of IL-1β but did not significantly induce the expression of angiogenic factors. MAT.Ang-1 alone did not induce leak or increase angiogenic factors but did reduce vascular endothelial growth factor expression in controls.ConclusionAdministration of MAT.Ang-1 after the onset of sepsis protects the microcirculation from endotoxemia-induced vascular dysfunction through reducing inflammation but without pro-angiogenic actions, thus representing a novel, potential pharmacotherapeutic agent for the treatment of sepsis.

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“…ALI/ARDS are syndromes of acute respiratory failure which occur as a series of malignancy attributed to diverse risk factors [ 17 ]. In spite of the advances in therapeutic principles and surgical techniques, ALI/ARDS still have high incidence and poor outcome, and ALI/ARDS continues to be a leading cause of morbidity and mortality in humans [ 18 ]. A20, known for many years as an anti-apoptotic protein through inhibiting the NF-κB signaling pathway, received attention in recent studies as an important negative regulator of inflammation [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Zinc Finger Protein A20 on Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation/Anti-Inflammatory Mediators in an Acute Lung Injury/Acute Respiratory Distress Syndrome Rat Model

Zhang

et al. 2017

Med Sci Monit

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BackgroundThe aim of this study was to investigate the effects of zinc finger protein A20 on lipopolysaccharide (LPS)-induced pulmonary inflammation/anti-inflammatory mediators in an acute lung injury/acute respiratory distress syndrome (ALI/ARDS) rat model.Material/MethodsForty-eight ALI/ARDS rats were selected and assigned into normal saline (NS) (injected with NS), LPS (injected with LPS), LPS-C1 (injected with pEGFP-C1, NS and LPS), and A20 groups (injected with pEGFP-C1-A20, NS, and LPS). The wet/dry (W/D) ratio of rat lung tissues and total protein concentration and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were detected. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were applied to detect the protein and mRNA expressions of A20, IL-10, and TNF-α, respectively. Western blotting was employed to detect the protein expressions of A20, nuclear factor-kappa B (NF-κB) p65 and NF-κB p-P65 in rat lung tissues.ResultsCompared with the NS group, the W/D ratio of rat lung tissues and total protein concentration and the number of neutrophils in BALF in the other 3 groups increased significantly. The protein and mRNA expressions of A20, IL-10, and TNF-α were significantly higher in the LPS group than in the NS group. The protein and mRNA expressions of A20 and IL-10 were significantly up-regulated and the expression of TNF-α, NF-κB p65, and NF-κB p-P65 was significantly down-regulated in rats injected with A20 compared to those in the LPS group.ConclusionsThe study provided evidence that zinc finger protein A20 can alleviate pulmonary inflammation by inhibiting TNF-α, NF-κB p65, and NF-κB p-P65 expressions and promoting IL-10 expression.

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Novel Interventional Approaches for ALI/ARDS: Cell-Based Gene Therapy

Cited by 16 publications

References 69 publications

Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-κB in Mice

Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-κB in Mice

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

Effects of Zinc Finger Protein A20 on Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation/Anti-Inflammatory Mediators in an Acute Lung Injury/Acute Respiratory Distress Syndrome Rat Model

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