scholarly journals NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs

1993 ◽  
Vol 2 (2) ◽  
pp. 135-141 ◽  
Author(s):  
J. M. Bator ◽  
A. M. Gillinov ◽  
K. J. Zehr ◽  
J. M. Redmond ◽  
I. C. Wilson ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Lung Injury ◽  
Lung Tissue ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Neutrophil Infiltration ◽  
Significant Inhibition ◽  
Cellular Infiltration ◽  
Lung Histology ◽  
Wet Weight

During cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement fragments C3a and C5a, leading to extravasation and subsequent tissue damage. In this study, the effects of the leumedin NPC 15669 (N [9H - (2,7 dimethylfluorenyl - 9 - methoxy) car bonyl]-L-leucine), a leukocyte recruitment inhibitor, were evaluated in a pig model of CPB. NPC 15669 caused significant inhibition of CPB associated increase in CD18 upregulation, lung tissue myeloperoxidase content, and percentage wet weight compared to controls. Lung histology revealed clear airways and minimal neutrophil infiltration in treated animals vs. significant oedema and cellular infiltration in controls. It is concluded that CPB causes a dramatic increase in neutrophil CD18, and that leumedins are effective in inhibiting neutrophil activation and subsequent tissue injury when administered during CPB.

scholarly journals Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung

2011 ◽  
Vol 300 (6) ◽  
pp. L930-L939 ◽  
Author(s):  
Songen Zhang ◽  
Milladur Rahman ◽  
Su Zhang ◽  
Zhongquan Qi ◽  
Heiko Herwald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Tissue Injury ◽  
Neutrophil Infiltration ◽  
Streptococcal Toxic Shock Syndrome ◽  
Edema Formation ◽  
M1 Protein ◽  
Cxcr2 Antagonist

Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung injury. Statins exert beneficial effects in septic patients although the mechanisms remain elusive. This study examined effects of simvastatin on M1 protein-provoked pulmonary inflammation and tissue injury. Male C57BL/6 mice were pretreated with simvastatin or a CXCR2 antagonist before M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for determination of neutrophil infiltration, formation of edema, and CXC chemokines. Flow cytometry was used to determine Mac-1 expression on neutrophils. Gene expression of CXC chemokines was determined in alveolar macrophages by using quantitative RT-PCR. M1 protein challenge caused massive infiltration of neutrophils, edema formation, and production of CXC chemokines in the lung as well as upregulation of Mac-1 on circulating neutrophils. Simvastatin reduced M1 protein-induced infiltration of neutrophils and edema in the lung. In addition, M1 protein-induced Mac-1 expression on neutrophils was abolished by simvastatin. Furthermore, simvastatin markedly decreased pulmonary formation of CXC chemokines and gene expression of CXC chemokines in alveolar macrophages. Moreover, the CXCR2 antagonist reduced M1 protein-induced neutrophil expression of Mac-1 and accumulation of neutrophils as well as edema formation in the lung. These novel findings indicate that simvastatin is a powerful inhibitor of neutrophil infiltration in acute lung damage triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil recruitment appears related to reduced pulmonary generation of CXC chemokines. Thus, simvastatin may be a useful tool to ameliorate acute lung injury in streptococcal infections.

scholarly journals Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf-2/HO-1 signal pathway

2020 ◽  
Author(s):  
Lin Fei ◽  
Xiao Jingyuan ◽  
Liang Fangte ◽  
Dai Huijun ◽  
Ye Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Alveolar Macrophages ◽  
Tissue Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lung Tissue Damage

Abstract Background Lung ischemia-reperfusion injury (LIRI) is a common and complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia-reperfusion (I/R). Oxidative stress reaction and antioxidant enzymes also play an important role in LIRI. This experiment was conducted to investigate whether preconditioning with rHMGB1 could ameliorate LIRI and explore the mechanisms of its protective effect in a lung I/R mice model. Methods Adult male mice were anesthetized and the left hilus pulmonis was clamped for 60 min, followed by 120 min of reperfusion. rHMGB1 was performed by intraperitoneal injection at 2 h before anesthesia. Brusatol (Nrf-2 antagonist) was given intraperitoneally every other day for a total of five times before surgery. Measurements of pathohistological lung tissue damage, pulmonary wet/dry (W/D) ratios, inflammatory mediators were performed to assess the extent of lung injury after I/R. Alveolar macrophages (AMs) pyroptosis were evaluated by LDH release, caspase-1 expression in flow cytometry, GSDMD expression in immunofluorescent staining. Measurement of the products of oxidative Stress (ROS, MDA, 15-F2t-Isoprostane) and the antioxidant enzymes (SOD, GSH-PX, CAT) were performed. Results Preconditioning with rHMGB1 significantly ameliorated I/R-induced lung injury through measuring the morphology, wet/dry weight ratio, the expressions of IL-1β, IL-6, NF-κB, HMGB1 in lung tissue. rHMGB1 preconditioning remarkably alleviated AMs pyroptosis induced by lung I/R. rHMGB1 preconditioning significantly reduced oxidative stress and restored the activity of antioxidative enzymes. In addition, rHMGB1 preconditioning mediated the activity of Keap1/Nrf-2/HO-1 pathway in LIRI. Furthermore, inhibiting Keap1/Nrf-2/HO-1 pathway through brusatol administration could aggravate lung tissue damage and inflammatory response after lung I/R. Also, brusatol administration could suppresse the antioxidant and anti-pyroptosis effects of rHMGB1 preconditioning in LIRI. Conclusions rHMGB1 preconditioning protects against LIRI through suppressing AMs pyroptosis. The mechanism is partially explained by inhibiting oxidative stress and improving the activity of antioxidative enzymes via Keap1/Nrf-2/HO-1 pathway.

scholarly journals Protective Effect of Corynoline in Sepsis-Induced Acute Lung Injury in Rats via Inhibition of NF-ĸB

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2096118
Author(s):  
Min Shu ◽  
Yulu Tang ◽  
Jianzhen Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
Significant Inhibition ◽  
Tissue Homogenate ◽  
Necrosis Factor Alpha ◽  
Lung Tissue Homogenate ◽  
And Migration

The present study was conducted to determine the effect of corynoline (COR) against sepsis-induced acute lung injury (ALI) in Wistar rats. Results of the study suggested that COR causes significant inhibition of lipid peroxidation (malondialdehyde) together with inhibition of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and myeloperoxidase). The level of various proinflammatory (tumor necrosis factor-alpha, interleukin-8, and migration inhibitory factor) was also found to be reduced in COR-treated rats after sepsis. The protective effect of COR was further substantiated by the histopathology of lung tissue, where it improves the architecture of alveolar spaces. In western blot analysis, COR causes significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells activation in the lung tissue homogenate. Our results demonstrated that COR was able to prevent the progression of ALI in rats via inhibition of inflammation and oxidative stress.

Curcumin therapy: Immune booster in present and post-pandemic (COVID-19) Era

2021 ◽  
Vol 12 (4) ◽  
pp. 2566-2572
Author(s):  
Shubha P ◽  
Shyamsundar S ◽  
Manjunatha H B
Keyword(s):  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
Therapeutic Agent ◽  
Tissue Injury ◽  
Curcuma Longa ◽  
Clinical Feature ◽  
World Population ◽  
Human Beings ◽  
Healthy Human

COVID-19 pandemic, which has traumatized the world population, in principle, is an inflammatory lung disease secondary to SARS-COV2 virus infection. Inflammatory lung injury progressing to Acute Respiratory Distress Syndrome (ARDS) is a recognized clinical feature of the disease. Inflammatory cytokines released in response to COVID-19 activate the transcription factor - the nuclear factor-қB (NF-қB) and series of pro-inflammatory cytokines, which are responsible for lung injury. Accurate yet precise treatment of coronavirus disease still remains inconclusive, and intervention is mainly symptomatic treatment, respiratory support, antiviral therapies and vaccination. Currently, the major focus of therapy is on reducing lung inflammation by elevating the host immunity. In this scenario, NF-қB inhibition can be conceptualized as a promising approach to down-regulate the overproduction of cytokines, such that inflammatory lung tissue injury could be prevented in COVID-19 infected patients. Towards this, curcumin from Curcuma longa (Turmeric) would play a vital role in the intervention and suppress NF-қB activation via translocation of p65 into the nucleus. Moreover, Curcumin is a proven therapeutic agent against various inflammatory pathologies as it also has the potential to inhibit the expression of certain genes that are critical for the regulation of inflammation.  Keeping this phenomenon and the current medical significance in view, we have explored and computed the anti-inflammatory properties of curcumin to develop it as a potent therapeutic agent to prevent NF-қB induced lung tissue injury in COVID-19 with the main goal of elevating immunity in the post-covid-19 situations as well as in healthy human beings.

Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage

2007 ◽  
Vol 292 (5) ◽  
pp. L1227-L1232 ◽  
Author(s):  
Ya-Ching Hsieh ◽  
Michael Frink ◽  
Chi-Hsun Hsieh ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Lung Injury ◽  
Migration Inhibitory Factor ◽  
Tissue Damage ◽  
Neutrophil Infiltration ◽  
Organ Damage ◽  
Inhibitory Factor ◽  
Sham Operation ◽  
Protective Effects ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1

Although studies have shown that 17β-estradiol (E2) prevents neutrophil infiltration and organ damage following trauma-hemorrhage, the mechanism by which E2inhibits neutrophil transmigration remains unknown. Macrophage migration inhibitory factor (MIF) is thought to play a central role in exacerbation of inflammation and is associated with lung injury. MIF regulates the inflammatory response through modulation of Toll-like receptor 4 (TLR4). Activation of TLR4 results in the release of proinflammatory cytokines and chemokines, which induce neutrophil infiltration and subsequent tissue damage. We hypothesized that E2mediates its salutary effects in the lung following trauma-hemorrhage via negative regulation of MIF and modulation of TLR4 and cytokine-induced chemotaxis. C3H/HeOuJ mice were subjected to trauma-hemorrhage (mean blood pressure 35 ± 5 mmHg for ∼90 min, then resuscitation) or sham operation. Mice received vehicle, E2, or E2in combination with recombinant mouse MIF protein (rMIF). Trauma-hemorrhage increased lung MIF and TLR4 protein levels as well as lung and systemic levels of cytokines/chemokines. Treatment of animals with E2following trauma-hemorrhage prevented these changes. However, administration of rMIF protein with E2abolished the E2-mediated decrease in lung TLR4 levels, lung and plasma levels of IL-6, TNF-α, monocyte chemoattractant protein-1, and keratinocyte-derived chemokine (KC). Administration of rMIF protein also prevented E2-mediated reduction in neutrophil influx and tissue damage in the lungs following trauma-hemorrhage. These results suggest that the protective effects of E2on lung injury following trauma-hemorrhage are mediated via downregulation of lung MIF and TLR4-induced cytokine/chemokine production.

scholarly journals Saquinavir Ameliorates Liver Warm Ischemia-Reperfusion-Induced Lung Injury via HMGB-1- and P38/JNK-Mediated TLR-4-Dependent Signaling Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhuang Yu ◽  
Yao Tong ◽  
Renlingzi Zhang ◽  
Xibing Ding ◽  
Quan Li
Keyword(s):  
Lung Injury ◽  
Signaling Pathways ◽  
Lung Tissue ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
High Mobility ◽  
Tissue Expression ◽  
Hiv Protease ◽  
Lung Edema ◽  
Beneficial Effects

Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is especially seen under uncontrolled aseptic inflammatory conditions, leading to injury of remote organs, such as lung injury, and even failure. Saquinavir (SQV) is a kind of HIV protease inhibitor that possesses an anti-inflammatory property. In this study, we investigated whether SQV suppresses Toll-like receptor 4- (TLR4-) dependent signaling pathways of high-mobility group box 1 (HMGB1) and P38/JNK, conferring protection against murine liver I/R-induced lung injury. To investigate our hypothesis, C57BL/6 mice and TLR4 knockout mice (TLR4−/−) were used to perform the study. SQV administration markedly attenuated remote lung tissue injury after 1-hour ischemia and 6-hour reperfusion of the liver. To our expectation, SQV attenuated I/R-induced lung edema, hyperpermeability, and pathological injury. The beneficial effects of SQV were associated with decreased levels of circulating and lung tissue inflammatory cytokines, such as IL-6, IL-1β, TNF-α, and iNOS. The protective effect of SQV was also associated with decreased lung tissue expression of HMGB1, TLR-4, and p-P38/JNK, but not p-ERK in wild-type liver I/R mice. Overall, this study demonstrated a new role of SQV, facilitating negative regulation of HMGB1- and P38/JNK-mediated TLR-4-dependent signaling pathways, conferring protection against liver I/R-induced lung injury.

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