scholarly journals Zoledronic acid targets the mevalonate pathway causing reduced cell recruitment and attenuation of pulmonary fibrosis

2021 ◽  
Author(s):  
Lloyd Tanner ◽  
Jesper Bergwik ◽  
Ravi Kiran Varma Bhongir ◽  
Arne Egesten
Keyword(s):  
Zoledronic Acid ◽  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Immune Cell ◽  
Mevalonate Pathway ◽  
Treatment Options ◽  
Lung Damage ◽  
Cell Recruitment ◽  
Efficacious Treatment ◽  
Immune Cell Recruitment

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreparable scarring of lung tissue, resulting in most patients succumbing rapidly after diagnosis. With limited treatment options available, repurposing of current pharmaceuticals offers an expeditious option to address this dire need. The mevalonate pathway, which is involved in the regulation of cell proliferation, survival and motility, is targeted by the bisphosphonate zoledronic acid (ZA). In this study, administration of ZA reduced myofibroblast transition and blocked NF-kB signaling in macrophages leading to impaired immune cell recruitment. ZA treatment of mice with bleomycin-induced lung damage displayed decreased levels of cytokines in the BALF, plasma, and lung tissue, resulting in less histologically visible fibrotic scarring. Additionally, bleomycin induced production of the ZA target, farnesyl diphosphate synthase (FDPS), was reduced in lung tissue and fibroblasts upon ZA treatment. Therefore, ZA administration offers an expedient and efficacious treatment option against IPF in a clinical setting.

scholarly journals In silico immune infiltration profiling reveals the role of naïve B cells in lung tissues of COVID-19 patients

2020 ◽  
Author(s):  
Yi-Lin Chiu ◽  
Yi-Ying Wu ◽  
Sheng-Huei Wang ◽  
Chih-Hsien Wu ◽  
Li-Chen Yen ◽  
...  
Keyword(s):  
B Cells ◽  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Immune Cells ◽  
Immune Cell ◽  
Severe Pneumonia ◽  
Lung Damage ◽  
Immune Infiltration ◽  
Humoral Immune ◽  
New Strategy

Abstract COVID-19 caused by SARS-CoV-2 has rapidly spread to more than 160 countries worldwide since 2020. Despite the tremendous efforts and resources spent around the world trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19. Approximately 15% of COVID-19 cases progress to pneumonia, patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). In addition, further pulmonary fibrosis from SARS-CoV-2 infection causes ARDS that often leads to irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily cause immune responses or immune cell infiltration can be identified, it is possible to alleviate or prevent severe lung damage by modulating the infiltration and activation of specific immune cells to mitigate excessive immunity response.The extent to which subsets of immune cells are significantly altered in the lung tissue of COVID-19 patients remains unclear. This study applied the CIBERSORT method to comprehensively evaluate the immune infiltration landscape in lung tissues of COVID-19 patients, and further compared with the one from lung tissue of patients with idiopathic pulmonary fibrosis (IPF). We found several immune cell subtypes; particularly naïve B cells are highly infiltrated in COVID-19 group. A comparison of functional gene set analysis revealed that non-differentiated naïve B cells may be the main cause of the overactive humoral immune response. We further compared several specific COVID-19 cases receiving therapies targeting B cells and found that appropriate suppression of naïve B cells might be a new strategy to alleviate severe symptoms of COVID-19.

scholarly journals A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

2021 ◽  
Vol 22 (3) ◽  
pp. 1118
Author(s):  
Abdulaziz Alamri ◽  
Derek Fisk ◽  
Deepak Upreti ◽  
Sam K. P. Kung
Keyword(s):  
Dendritic Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Viral Disease ◽  
Cell Recruitment ◽  
Cross Presentation ◽  
Cell Immunity ◽  
Immune Cell Recruitment

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

scholarly journals Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ruth Seelige ◽  
Robert Saddawi-Konefka ◽  
Nicholas M. Adams ◽  
Gaëlle Picarda ◽  
Joseph C. Sun ◽  
...  
Keyword(s):  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Mcmv Infection ◽  
Cell Recruitment ◽  
Immune Cell Recruitment

scholarly journals Non-Coding RNAs in COVID-19: Emerging Insights and Current Questions

2021 ◽  
Vol 7 (3) ◽  
pp. 54
Author(s):  
Tobias Plowman ◽  
Dimitris Lagos
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Cell ◽  
Cytokine Storm ◽  
Cell Recruitment ◽  
Vascular Dysregulation ◽  
Virus Rna ◽  
Growing Body ◽  
Non Coding Rnas ◽  
Immune Cell Recruitment

The highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, igniting an unprecedented pandemic. A mechanistic picture characterising the acute immunopathological disease in severe COVID-19 is developing. Non-coding RNAs (ncRNAs) constitute the transcribed but un-translated portion of the genome and, until recent decades, have been undiscovered or overlooked. A growing body of research continues to demonstrate their interconnected involvement in the immune response to SARS-CoV-2 and COVID-19 development by regulating several of its pathological hallmarks: cytokine storm syndrome, haemostatic alterations, immune cell recruitment, and vascular dysregulation. There is also keen interest in exploring the possibility of host–virus RNA–RNA and RNA–RBP interactions. Here, we discuss and evaluate evidence demonstrating the involvement of short and long ncRNAs in COVID-19 and use this information to propose hypotheses for future mechanistic and clinical studies.

scholarly journals Mesenchymal Cells Hold the Key to Immune Cell Recruitment to and Migration within Melanoma

2013 ◽  
Vol 133 (9) ◽  
pp. 2138-2140
Author(s):  
Kimberley A. Beaumont ◽  
Marcia A. Munoz ◽  
Wolfgang Weninger
Keyword(s):  
Immune Cell ◽  
Mesenchymal Cells ◽  
Cell Recruitment ◽  
And Migration ◽  
Immune Cell Recruitment

Canephron N reduced immune cell recruitment in experimental cystitis

2017 ◽  
Vol 16 (3) ◽  
pp. e230-e231 ◽  
Author(s):  
B. Nausch ◽  
J. Röhrl ◽  
A. Koeberle ◽  
U. Harler ◽  
M. Joannidis ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Recruitment ◽  
Immune Cell Recruitment
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