Pulmonary Innate Immune Response Determines the Outcome of Inflammation During Pneumonia and Sepsis-Associated Acute Lung Injury

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 4, 2020

The lung is a primary organ for gas exchange in mammals that represents the largest epithelial surface direct contact with external environment. It also serves as crucial immune organ, which harbors both innate and adaptive cells to induce potent response. Due its outer environment, target many airborne pathogens, toxicants (aerosols), allergens causing pneumonia, acute respiratory distress syndrome (ARDS), injury or inflammation (ALI). current review describes immunological mechanisms responsible bacterial pneumonia sepsis-induced ALI. highlights differences severity of ALI compared pneumonia-associated immune-based between Gram-positive Gram-negative bacteria-induced show different role pulmonary (PECs), alveolar macrophages (AMs), lymphoid (ILCs), pattern-recognition receptors (PRRs, including Toll-like (TLRs) inflammasome proteins) neutrophil infiltration induction have been described during Also, resolution frequently observed associated whereas sepsis-associated lacks it. Hence, mainly response depending on causal pathogen (Gram-positive bacteria) should be taken mind specific therapeutics.

Language: Английский

---

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

Pharmacological Research, Journal Year: 2020, Volume and Issue: 163, P. 105224 - 105224

Published: Sept. 29, 2020

Language: Английский

---

Quercetin Prevents LPS-Induced Oxidative Stress and Inflammation by Modulating NOX2/ROS/NF-kB in Lung Epithelial Cells

Molecules, Journal Year: 2021, Volume and Issue: 26(22), P. 6949 - 6949

Published: Nov. 17, 2021

Oxidative stress caused by the production of reactive oxygen species (ROS) plays a major role in inflammatory processes. We hypothesized that modulation ROS via quercetin may protect against oxidative and inflammation. Thus, this study aimed to investigate effects on inflammation lung epithelial A549 cells. The lipopolysaccharide (LPS)-induced elevation intracellular levels was reduced after treatment, which also almost completely abolished mRNA protein expression nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) induced LPS stimulation. In addition, suppressed nuclear translocation factor kappa B (NF-κB) cytokine tumor necrosis (TNF)-α, interleukin (IL)-1, IL-6, had increased significantly exposure. Our data demonstrated decreased ROS-induced suppressing NOX2 production.

Language: Английский

---

Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential

The Journal of Pathology, Journal Year: 2018, Volume and Issue: 247(5), P. 672 - 685

Published: Dec. 20, 2018

Abstract Acute respiratory distress syndrome (ARDS) is the often fatal sequelae of a broad range precipitating conditions. Despite decades intensive research and clinical trials there remain no therapies in routine practice that target dysregulated overwhelming inflammatory response characterises ARDS. Neutrophils play central role initiation, propagation resolution this complex environment by migrating into lung executing variety pro‐inflammatory functions. These include degranulation with liberation bactericidal proteins, release cytokines reactive oxygen species as well production neutrophil extracellular traps. Although these functions are advantageous clearing bacterial infection, consequence associated tissue damage, contribution to worsening acute inflammation prolonged lifespan at sites deleterious. In review, importance will be considered, together discussion recent advances understanding function factors influence them throughout phases From better neutrophils context, potential therapeutic targets identified discussed. © 2018 The Authors. Journal Pathology published John Wiley & Sons Ltd on behalf Pathological Society Great Britain Ireland.

Language: Английский

---

Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression

Advances in Biological Regulation, Journal Year: 2020, Volume and Issue: 77, P. 100741 - 100741

Published: July 4, 2020

Pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome 2 (SARS-CoV-2) and poses an unprecedented challenge to healthcare systems due the lack of a vaccine specific treatment options. Accordingly, there urgent need understand precisely pathogenic mechanisms underlying this multifaceted disease. There increasing evidence that immune system reacts insufficiently SARS-CoV-2 thus contributes organ damage lethality. In review, we suggest overwhelming production reactive oxygen species (ROS) resulting in oxidative stress major cause local or systemic tissue leads COVID-19. It increases formation neutrophil extracellular traps (NETs) suppresses adaptive arm system, i.e. T cells are necessary kill virus-infected cells. This creates vicious cycle prevents response against SARS-CoV-2. The key role pathogenesis COVID-19 implies therapeutic counterbalancing ROS antioxidants such as vitamin C NAC and/or antagonizing mononuclear phagocyte (MPS) granulocytes blocking TNF-α can prevent from becoming severe. Controlled clinical trials preclinical models needed evaluate hypothesis.

Language: Английский

---

Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury

ACS Central Science, Journal Year: 2021, Volume and Issue: 8(1), P. 10 - 21

Published: Dec. 2, 2021

Pneumonia, such as acute lung injury (ALI), has been a type of lethal disease that is generally caused by uncontrolled inflammatory response and excessive generation reactive oxygen species (ROS). Herein, we report Fe-curcumin-based nanoparticles (Fe-Cur NPs) with nanozyme functionalities in guiding the intracellular ROS scavenging meanwhile exhibiting anti-inflammation efficacy for curing ALI. The are noncytotoxic when directing these biological activities. Mechanism studies aspects Fe-Cur NPs were systematically carried out, which infected cells tissues alleviated through downregulating levels several important cytokines (such TNF-α, IL-1β, IL-6), decreasing Ca2+ release, inhibiting NLRP3 inflammasomes, suppressing NF-κB signaling pathways. In addition, performed both intratracheal intravenous injection mice experiencing ALI and, importantly, found accumulation nanozymes was enhanced tissue (better than free curcumin drugs), demonstrating its promising therapeutic efficiency two different administration methods. We showed inflammation reduction effective animal experiments also effectively achieved tissue. Finally, revealed can decrease level macrophage (CD11bloF4/80hi) CD3+CD45+ T mice, could help suppress cytokine storm Overall, this work developed strategy using to scavenge an nanodrugs synergistically cure ALI, may serve agent clinical treatment deadly disease. NP designed attenuate clearing alleviating synergistically. Relevant cytokines, pathways studied.

Language: Английский

---

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(2), P. 600 - 620

Published: Aug. 12, 2021

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify expression pro-inflammatory cytokines and chemokines at mRNA level. properties such as clear anatomy, accessibility, relatively low enzyme activity make a good target local therapy. However, translation is restricted by inefficient delivery therapeutics cells due naked siRNA. Thus, this review will focus on various systems that can used different barriers need surmounted development stable inhalable formulations human before ALI/ARDS become available in clinic.

Language: Английский

---

Understanding the role of neutrophils in acute respiratory distress syndrome

Biomedical Journal, Journal Year: 2020, Volume and Issue: 44(4), P. 439 - 446

Published: Sept. 10, 2020

Acute respiratory distress syndrome (ARDS) is difficult to treat and associated with a high mortality rate. The most severe form of coronavirus disease 2019 (COVID-19) also leads life-threatening ARDS. Neutrophil counts are positively correlated severity in activation not only plays significant role immune defense against infections, but causes tissue damage inflammatory diseases. Activated neutrophils rapidly migrate inflamed lung tissue, releasing toxic granular contents generating neutrophil extracellular traps. In the last few decades, it has become apparent that occupy central ARDS pathology. this review, we summarize responses their relationships According current literature, understanding function may be helpful treatment

Language: Английский

---

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: June 23, 2020

Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in infection, the contribution of NK fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology therapeutic opportunities can therefore be inferred from studies assessing cell phenotype function during SARS, MERS, COVID-19. These suggest a reduction circulating numbers and/or an exhausted following infection hint towards dampening responses by coronaviruses. Reduced levels exhaustion may responsible progression severity Conversely, light data linking inflammation with coronavirus disease severity, it is necessary to examine potential mediating immunopathology. A common feature infections that significant morbidity mortality associated lung injury acute respiratory distress syndrome resulting exaggerated response, which important component. In this review, we summarize current understanding how respond both early late infections, implication ongoing COVID-19 clinical trials. Using immunological lens, outline recommendations strategies against clearing virus while preventing harm immunopathological responses.

Language: Английский

---

Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Dec. 7, 2021

Abstract Oxidative stress contributes to the pathogenesis of acute lung injury. Protein S-glutathionylation plays an important role in cellular antioxidant defense. Here we report that expression deglutathionylation enzyme Grx1 is decreased lungs injury mice. The induced by hyperoxia or LPS significantly relieved KO and fl/fl LysM cre mice, confirming protective Grx1-regulated macrophages. Using a quantitative redox proteomics approach, show FABP5 susceptible under oxidative conditions. Cys127 promotes its fatty acid binding ability nuclear translocation. Further results indicate interaction PPARβ/δ, activates PPARβ/δ target genes suppresses LPS-induced inflammation Our study reveals molecular mechanism through which regulates macrophage

Language: Английский

---