scholarly journals Transduced PEP-1-Heme Oxygenase-1 Fusion Protein Attenuates Lung Injury in Septic Shock Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Xue-Tao Yan ◽  
Xiang-Hu He ◽  
Yan-Lin Wang ◽  
Zong-Ze Zhang ◽  
Jun-Jiao Tang
Keyword(s):  
Oxidative Stress ◽  
Septic Shock ◽  
Lung Injury ◽  
Fusion Protein ◽  
Heme Oxygenase ◽  
Cecal Ligation ◽  
Protective Role ◽  
Lung Damage ◽  
Heme Oxygenase 1 ◽  
Anti Inflammatory

Oxidative stress and inflammation have been identified to play a vital role in the pathogenesis of lung injury induced by septic shock. Heme oxygenase-1 (HO-1), an effective antioxidant and anti-inflammatory and antiapoptotic substance, has been used for the treatment of heart, lung, and liver diseases. Thus, we postulated that administration of exogenous HO-1 protein transduced by cell-penetrating peptide PEP-1 has a protective role against septic shock-induced lung injury. Septic shock produced by cecal ligation and puncture caused severe lung damage, manifested in the increase in the lung wet/dry ratio, oxidative stress, inflammation, and apoptosis. However, these changes were reversed by treatment with the PEP-1-HO-1 fusion protein, whereas lung injury in septic shock rats was alleviated. Furthermore, the septic shock upregulated the expression of Toll-like receptor 4 (TLR4) and transcription factor NF-κB, accompanied by the increase of lung injury. Administration of PEP-1-HO-1 fusion protein reversed septic shock-induced lung injury by downregulating the expression of TLR4 and NF-κB. Our study indicates that treatment with HO-1 protein transduced by PEP-1 confers protection against septic shock-induced lung injury by its antioxidant, anti-inflammatory, and antiapoptotic effects.

Class B Scavenger Receptors BI and BII Protect Against LPS-induced Acute Lung Injury in Mice by Mediating LPS Clearance

2021 ◽  
Author(s):  
Irina N. Baranova ◽  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Zhigang Chen ◽  
Anna A. Birukova ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Protective Role ◽  
Lung Damage ◽  
Wild Type ◽  
Class B ◽  
Anti Inflammatory

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake, and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates understanding SR-BI’s role in endotoxemia/sepsis, calling for use of alternative models. In this study, using hSR-BI and hSR-BII transgenic mice, we found that SR-BI and to a lesser extent its splicing variant SR-BII, protects against LPS-induced lung damage. At 20 hours after intratracheal LPS instillation the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content as well as lung tissue neutrophil infiltration found in wild type mice was associated with markedly (2-3 times) increased pro-inflammatory cytokine production as compared to transgenic mice following LPS administration. Markedly lower endotoxin levels detected in BALF of transgenic vs. wild type mice along with the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection suggest that hSR-BI and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.

scholarly journals Involvement of Heme Oxygenase-1 Induction in the Cytoprotective and Immunomodulatory Activities ofViola patriniiin Murine Hippocampal and Microglia Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Li ◽  
Dong-Sung Lee ◽  
Hyun-Gyu Choi ◽  
Kyoung-Su Kim ◽  
Gil-Saeng Jeong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Reactive Oxygen Species Generation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ht22 Cells ◽  
Proinflammatory Mediators ◽  
Bv2 Cells ◽  
Anti Inflammatory

A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract ofViola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-αand interleukin-1β). Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

scholarly journals Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury

1999 ◽  
Vol 277 (6) ◽  
pp. L1214-L1223 ◽  
Author(s):  
Funmei Yang ◽  
Jacqueline J. Coalson ◽  
Heather H. Bobb ◽  
Jacqueline D. Carter ◽  
Jameela Banu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Lung Damage ◽  
Mouse Lung ◽  
Heme Oxygenase 1 ◽  
Wild Type ◽  
Chronic Pulmonary Diseases ◽  
Hyperoxic Lung Injury ◽  
Key Participants

Oxidative stress plays a central role in the pathogenesis of acute and chronic pulmonary diseases. Safe sequestration of iron, which participates in the formation of the hydroxyl radical, is crucial in the lung's defense. We used a mouse line defective in the major iron transport protein transferrin to investigate the effect of aberrant iron metabolism on the lung's defense against oxidative injury. The tolerance to hyperoxic lung injury was greater in the hypotransferrinemic than in wild-type mice as documented by histopathology and biochemical indexes for lung damage. There was no increase in the levels of intracellular antioxidants, inflammatory cytokines, and heme oxygenase-1 in the hypotransferrinemic mouse lung compared with those in wild-type mice. However, there were elevated expressions of ferritin and lactoferrin in the lung of hypotransferrinemic mice, especially in the alveolar macrophages. Our results suggest that pulmonary lactoferrin and ferritin protect animals against oxidative stress, most likely via their capacity to sequester iron, and that alveolar macrophages are the key participants in iron detoxification in the lower respiratory tract.

scholarly journals Vasculoprotective effects of heme oxygenase-1 in a murine model of hyperoxia-induced bronchopulmonary dysplasia

2012 ◽  
Vol 302 (8) ◽  
pp. L775-L784 ◽  
Author(s):  
Angeles Fernandez-Gonzalez ◽  
S. Alex Mitsialis ◽  
Xianlan Liu ◽  
Stella Kourembanas
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Heme Oxygenase ◽  
Ventricular Hypertrophy ◽  
Iron Homeostasis ◽  
Pulmonary Inflammation ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Protective Mechanisms ◽  
Vascular Growth ◽  
Anti Inflammatory

Bronchopulmonary dysplasia (BPD) is characterized by simplified alveolarization and arrested vascular development of the lung with associated evidence of endothelial dysfunction, inflammation, increased oxidative damage, and iron deposition. Heme oxygenase-1 (HO-1) has been reported to be protective in the pathogenesis of diseases of inflammatory and oxidative etiology. Because HO-1 is involved in the response to oxidative stress produced by hyperoxia and is critical for cellular heme and iron homeostasis, it could play a protective role in BPD. Therefore, we investigated the effect of HO-1 in hyperoxia-induced lung injury using a neonatal transgenic mouse model with constitutive lung-specific HO-1 overexpression. Hyperoxia triggered an increase in pulmonary inflammation, arterial remodeling, and right ventricular hypertrophy that was attenuated by HO-1 overexpression. In addition, hyperoxia led to pulmonary edema, hemosiderosis, and a decrease in blood vessel number, all of which were markedly improved in HO-1 overexpressing mice. The protective vascular response may be mediated at least in part by carbon monoxide, due to its anti-inflammatory, antiproliferative, and antiapoptotic properties. HO-1 overexpression, however, did not prevent alveolar simplification nor altered the levels of ferritin and lactoferrin, proteins involved in iron binding and transport. Thus the protective mechanisms elicited by HO-1 overexpression primarily preserve vascular growth and barrier function through iron-independent, antioxidant, and anti-inflammatory pathways.

scholarly journals Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury

1998 ◽  
Vol 274 (4) ◽  
pp. L582-L590 ◽  
Author(s):  
Jennifer L. Taylor ◽  
Martha Sue Carraway ◽  
Claude A. Piantadosi
Keyword(s):  
Oxidative Stress ◽  
Enzyme Activity ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Normal Saline ◽  
Dry Weight ◽  
Heme Oxygenase 1 ◽  
Specific Induction ◽  
Hyperoxic Lung Injury ◽  
Tin Protoporphyrin

Heme oxygenase (HO)-1, which catalyzes heme breakdown, is induced by oxidative stress and may protect against oxidative injury. We hypothesized that induction of HO-1 by hemoglobin (Hb) in the lung would protect the rat from pulmonary O2 toxicity. Rats given intratracheal (IT) Hb showed lung-specific induction of HO-1 by 8 h by Western analysis. Rats were then pretreated for 8 h before 60 h of exposure to 100% O2 with either IT normal saline, Hb, or Hb plus the HO-1 inhibitor tin-protoporphyrin (SnPP). Both the Hb+O2 and Hb+O2+ SnPP animals had less lung injury than normal saline controls as indicated by lower pleural fluid volumes and wet-to-dry weight ratios ( P < 0.01). The improvement in injury in the two Hb-treated groups was the same despite a 61% decrease in HO enzyme activity in the Hb+SnPP group after 60 h of O2. In addition, inhibition of HO activity with SnPP alone before O2exposure did not augment the extent of hyperoxic lung injury. These results demonstrate that IT Hb induces lung HO-1 in the rat and protects against hyperoxia; however, the protection is not mediated by increased HO enzyme activity.

scholarly journals Pterostilbene 4′-β-Glucoside Attenuates LPS-Induced Acute Lung Injury via Induction of Heme Oxygenase-1

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Jeongmin Park ◽  
Yingqing Chen ◽  
Min Zheng ◽  
Jinhyun Ryu ◽  
Gyeong Jae Cho ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mouse Lung ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Protective Effects ◽  
Anti Inflammatory

Heme oxygenase-1 (HO-1) can exert anti-inflammatory and antioxidant effects. Acute lung injury (ALI) is associated with increased inflammation and influx of proinflammatory cells and mediators in the airspaces and lung parenchyma. In this study, we demonstrate that pterostilbene 4′-β-glucoside (4-PG), the glycosylated form of the antioxidant pterostilbene (PTER), can protect against lipopolysaccharide- (LPS-) orPseudomonas aeruginosa- (P. aeruginosa-) induced ALI when applied as a pretreatment or therapeutic post-treatment, via the induction of HO-1. To determine whether HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG, we subjected mice genetically deficient inHmox-1to LPS-induced ALI and evaluated histological changes, HO-1 expression, and proinflammatory cytokine levels in bronchoalveolar lavage (BAL) fluid. 4-PG exhibited protective effects on LPS- orP. aeruginosa-induced ALI by ameliorating pathological changes in lung tissue and decreasing proinflammatory cytokines. In addition, HO-1 expression was significantly increased by 4-PG in cells and in mouse lung tissues. The glycosylated form of pterostilbene (4-PG) was more effective than PTER in inducing HO-1 expression. Genetic deletion ofHmox-1abolished the protective effects of 4-PG against LPS-induced inflammatory responses. Furthermore, we found that 4-PG decreased both intracellular ROS levels and mitochondrial (mt) ROS production in a manner dependent on HO-1. Pharmacological application of the HO-1 reaction product carbon monoxide (CO), but not biliverdin or iron, conferred protection inHmox-1-deficient macrophages. Taken together, these results demonstrate that 4-PG can increase HO-1 expression, which plays a critical role in ameliorating intracellular and mitochondrial ROS production, as well as in downregulating inflammatory responses induced by LPS. Therefore, these findings strongly suggest that HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG.

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