scholarly journals Review: Toll-like receptors and NOD-like receptors in pulmonary antibacterial immunity

2010 ◽  
Vol 16 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Theivanthiran Balamayooran ◽  
Gayathriy Balamayooran ◽  
Samithamby Jeyaseelan
Keyword(s):  
Distress Syndrome ◽  
Bacterial Pathogens ◽  
Treatment Strategies ◽  
Lung Damage ◽  
Toll Like Receptors ◽  
Neutrophil Accumulation ◽  
Cellular Mechanisms ◽  
Neutrophil Influx ◽  
Life Threatening ◽  
Parenchymal Damage

Lung diseases caused by bacteria are a leading cause of death in both immunocompromised and immunocompetent individuals as well as in children. Although neutrophil recruitment is critical to augment the host defence, excessive neutrophil accumulation results in life-threatening diseases, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Therefore, it is important to modulate excessive neutrophil influx in ALI/ARDS to mitigate lung damage and mortality. A better understanding of the basic mechanisms underlying neutrophil influx is crucial to designing novel and innovative treatment strategies for ALI/ARDS. Recognition of bacteria in the lung is the critical first step leading to neutrophil influx. Pattern recognition receptors, such as Toll-like receptors and NOD-like receptors, play an important role in the recognition of bacterial pathogens. Understanding the molecular and cellular mechanisms associated with the recognition of bacterial pathogens by the host is critical for the development of effective therapeutic strategies to control parenchymal damage via modulating neutrophil accumulation in the lung.

scholarly journals Transcriptional Profiling of Lipopolysaccharide-Induced Acute Lung Injury

2004 ◽  
Vol 72 (12) ◽  
pp. 7247-7256 ◽  
Author(s):  
Samithamby Jeyaseelan ◽  
Hong Wei Chu ◽  
Scott K. Young ◽  
G. Scott Worthen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transcriptional Profiling ◽  
Lung Damage ◽  
Neutrophil Accumulation ◽  
Transcriptional Responses ◽  
Necrosis Factor Alpha ◽  
Neutrophil Influx ◽  
Inflammatory Genes ◽  
Proinflammatory Mediators

ABSTRACT Mortality associated with acute lung injury (ALI) induced by lipopolysaccharide (LPS) remains high in humans, warranting improved treatment and prevention strategies. ALI is characterized by the expression of proinflammatory mediators and extensive neutrophil influx into the lung, followed by severe lung damage. Understanding the pathogenesis of LPS-induced ALI is a prerequisite for designing better therapeutic strategies. In the present study, we used microarrays to gain a global view of the transcriptional responses of the lung to LPS in a mouse model of ALI that mimics ALI in humans. A total of 71 inflammation-associated genes were up-regulated in LPS-treated lungs, including a chemokine, LPS-induced CXC chemokine (LIX), whose role in the induction of ALI is unknown. Most of the inflammatory genes peaked at 2 h post-LPS treatment. Real-time reverse transcription-PCR confirmed the LPS-induced up-regulation of selected genes identified by microarray analysis, including LIX. The up-regulation of LIX, tumor necrosis factor alpha, and macrophage inflammatory protein 2 was confirmed at the protein level by enzyme-linked immunosorbent assays. To determine the role of LIX in the induction of ALI, we used both exogenous LIX and a LIX blocking antibody. Exogenous LIX alone elicited a neutrophil influx in the lungs, and the anti-LIX antibody attenuated the LPS-induced neutrophil accumulation in the lungs. Taken together, the results of our study demonstrate for the first time the temporal expression of inflammatory genes during LPS-induced ALI and suggest that early therapeutic intervention is crucial to attenuate lung damage. Moreover, we identified a role for LIX in the induction of ALI, and therefore LIX may serve as a novel therapeutic target for the minimization of ALI.

scholarly journals The Features of Pathobiology and Clinical translation of Approved treatments for Coronavirus Disease 2019 (COVID-19)

Intervirology ◽  
2021 ◽  
Author(s):  
Hamidreza Abbasi ◽  
Hadi Razavi Nikoo ◽  
Ali Fallah ◽  
Azadeh Mohammad-Hasani ◽  
Abasalt Hosseinzadeh Colagar ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Transmission Rate ◽  
Treatment Strategies ◽  
Etiological Agent ◽  
Behavioral Factors ◽  
Cellular Mechanisms

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last two years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, is another factor. Summary: In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. Key Messages: We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.

scholarly journals Regulation of PTEN activity by p38δ-PKD1 signaling in neutrophils confers inflammatory responses in the lung

2012 ◽  
Vol 209 (12) ◽  
pp. 2229-2246 ◽  
Author(s):  
Arne Ittner ◽  
Helena Block ◽  
Christoph A. Reichel ◽  
Markku Varjosalo ◽  
Helmuth Gehart ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
Inflammatory Responses ◽  
Neutrophil Migration ◽  
P38 Map Kinase ◽  
Neutrophil Accumulation ◽  
Protein Kinase D1 ◽  
Downstream Target ◽  
Life Threatening

Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating in acute respiratory distress syndrome (ARDS), a frequent complication with high mortality in humans. Molecular mechanisms underlying recruitment of neutrophils to sites of inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required for recruitment of neutrophils into inflammatory sites. Global and myeloid-restricted deletion of p38δ in mice results in decreased alveolar neutrophil accumulation and attenuation of ALI. p38δ counteracts the activity of its downstream target protein kinase D1 (PKD1) in neutrophils and myeloid-restricted inactivation of PKD1 leads to exacerbated lung inflammation. Importantly, p38δ and PKD1 conversely regulate PTEN activity in neutrophils, thereby controlling their extravasation and chemotaxis. PKD1 phosphorylates p85α to enhance its interaction with PTEN, leading to polarized PTEN activity, thereby regulating neutrophil migration. Thus, aberrant p38δ–PKD1 signaling in neutrophils may underlie development of ALI and life-threatening ARDS in humans.

A Review of the Therapeutic Benefits of Moringa oleifera in Controlling High Blood Pressure (Hypertension)

2019 ◽  
Vol 5 (3) ◽  
pp. 232-245
Author(s):  
Chuku Okorie ◽  
Kola Ajibesin ◽  
Adekunle Sanyaolu ◽  
Adeena Islam ◽  
Selciya Lamech ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Moringa Oleifera ◽  
Kidney Diseases ◽  
Treatment Strategies ◽  
Secondary Hypertension ◽  
Therapeutic Benefits ◽  
Northern Regions ◽  
Long Time ◽  
Life Threatening

Moringa oleifera (M. oleifera) is an angiosperm plant that is a member of the Moringaceae family. It is a natural plant that is native to the sub-Himalayan northern regions of India, Bangladesh, Pakistan, and Afghanistan. The plant grows abundantly throughout tropical and subtropical areas of the world. For several centuries, many cultures have utilized various parts of the moringa plant as traditional medicine to treat common illnesses and control life-threatening conditions such as hypertension (HTN), diabetes, hyperlipidemia, inflammation, etc. This article reviewed the current literature on the therapeutic benefits of M. oleifera on hypertension, primarily focusing on identifying the plant’s key components and its roles in hindering the common pathophysiological pathways associated with hypertension. The number of people living with HTN has been predicted to increase to 1.56 billion worldwide by 2025 in spite of the myriads of preventive and treatment strategies available today. Therefore, it would be of great value to explore alternative complementary ways of controlling high blood pressure. HTN is commonly defined as blood pressure equal to or higher than 140/90 mm Hg. HTN itself is not a disease condition and does not elicit specific symptoms, however, if left untreated for a long time, it can lead to complicated cardiovascular diseases such as angina, congestive heart failure, myocardial infarction as well as stroke and chronic kidney diseases. Primary hypertension is diagnosed when there is no known identifiable underlying cause for the onset of the condition. Secondary hypertension is diagnosed when there is evidence of a disease or disorder triggering the onset of the condition. It is apparent that understanding the role of M. oleifera in the management of hypertension would expand the valuable strategies for the control of this condition.

scholarly journals Fast-Onset Diffuse Interstitial Lung Disease in Anti-MDA5 Antibodies-Associated Amyopathic Dermatomyositis

2021 ◽  
Vol 11 (2) ◽  
pp. 235-240
Author(s):  
Houari Aissaoui ◽  
Kinan Drak Alsibai ◽  
Naji Khayath
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Distress Syndrome ◽  
Early Stage ◽  
Immunosuppressive Treatment ◽  
Amyopathic Dermatomyositis ◽  
Pulmonary Manifestations ◽  
Life Threatening ◽  
Adequate Management ◽  
Chest Ct Scan

Anti-MDA5 antibodies-associated amyopathic dermatomyositisis a rare autoimmune disease that involve polyarthritis, cutaneous and pulmonary manifestations. The development of rapidly progressing interstitial lung disease is a life-threatening complication. We report the case of a 45-year-old woman without medical history, who was addressed to the Pulmonary Department for a polyarthritis with dry cough and hypoxemic dyspnea. Initially there was neither cutaneous manifestation nor interstitial lung disease on chest CT scan. After a few days, the patient developed fatal acute respiratory failure with diffuse ground glass opacities. Identification of anti-MDA5 antibodies allowed establishing diagnosis, despite the fact that the first immunological assessment was negative. Corticosteroid bolus of 1 g for three days and immunosuppressive treatment by cyclophosphamide was only initiated at the acute respiratory distress syndrome stage. Given the rapidly unfavorable prognosis of this entity of amyopathic dermatomyositis, the testing for anti-MDA5 antibodies should be recommended in case of progressive pulmonary symptoms associated with joint signs in order to identify this disease at an early stage and to begin rapid and adequate management.

scholarly journals Management of ST Elevation Myocardial Infarction (STEMI) in Different Settings

2021 ◽  
Author(s):  
Rod Partow-Navid ◽  
Narut Prasitlumkum ◽  
Ashish Mukherjee ◽  
Padmini Varadarajan ◽  
Ramdas G. Pai
Keyword(s):  
Myocardial Infarction ◽  
Treatment Strategies ◽  
Management Process ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
Multiple Factors ◽  
St Segment ◽  
Threatening Condition ◽  
Life Threatening ◽  
St Elevation

AbstractST-segment elevation myocardial infarction (STEMI) is a life-threatening condition that requires emergent, complex, well-coordinated treatment. Although the primary goal of treatment is simple to describe—reperfusion as quickly as possible—the management process is complicated and is affected by multiple factors including location, patient, and practitioner characteristics. Hence, this narrative review will discuss the recommended management and treatment strategies of STEMI in the circumstances.

scholarly journals Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

2021 ◽  
Vol 22 (6) ◽  
pp. 3059
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Eugenio Garofalo ◽  
Andrea Bruni ◽  
Alessandro Vatrella ◽  
...  
Keyword(s):  
Review Article ◽  
Lung Damage ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Cytokine Storm ◽  
Future Perspectives ◽  
Pathogenic Role ◽  
Refractory Rheumatoid Arthritis ◽  
Life Threatening

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals The Phosphoarginine Phosphatase PtpB from Staphylococcus aureus Is Involved in Bacterial Stress Adaptation during Infection

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 645
Author(s):  
Mohamed Ibrahem Elhawy ◽  
Sylvaine Huc-Brandt ◽  
Linda Pätzold ◽  
Laila Gannoun-Zaki ◽  
Ahmed Mohamed Mostafa Abdrabou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Treatment Strategies ◽  
Physiological Role ◽  
Aureus Strain ◽  
Stress Adaptation ◽  
Cellular Mechanisms ◽  
Host Interaction ◽  
Liver And Kidney

Staphylococcus aureus continues to be a public health threat, especially in hospital settings. Studies aimed at deciphering the molecular and cellular mechanisms that underlie pathogenesis, host adaptation, and virulence are required to develop effective treatment strategies. Numerous host-pathogen interactions were found to be dependent on phosphatases-mediated regulation. This study focused on the analysis of the role of the low-molecular weight phosphatase PtpB, in particular, during infection. Deletion of ptpB in S. aureus strain SA564 significantly reduced the capacity of the mutant to withstand intracellular killing by THP-1 macrophages. When injected into normoglycemic C57BL/6 mice, the SA564 ΔptpB mutant displayed markedly reduced bacterial loads in liver and kidney tissues in a murine S. aureus abscess model when compared to the wild type. We also observed that PtpB phosphatase-activity was sensitive to oxidative stress. Our quantitative transcript analyses revealed that PtpB affects the transcription of various genes involved in oxidative stress adaptation and infectivity. Thus, this study disclosed first insights into the physiological role of PtpB during host interaction allowing us to link phosphatase-dependent regulation to oxidative bacterial stress adaptation during infection.

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