Journal of Inflammation-London最新文献

{"title":"Identification and validation of biomarkers related to Th1 cell infiltration in neuropathic pain.","authors":"Xiangsheng Zhang,&nbsp;Jiurong Cheng,&nbsp;Yingdong Deng,&nbsp;Caiyun Guo,&nbsp;Yu Cao,&nbsp;Suo Wang,&nbsp;Chenxi Zhou,&nbsp;Ziqiang Lin,&nbsp;Simin Tang,&nbsp;Jun Zhou","doi":"10.1186/s12950-023-00343-0","DOIUrl":"https://doi.org/10.1186/s12950-023-00343-0","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a widespread chronic pain with a prevalence of 6.9-10% in the general population, severely affecting patients' physical and mental health. Accumulating evidence indicated that the immune environment is an essential factor causing NP. However, the mechanism is unclear. This study attempted to analyze NP-related immune infiltration patterns. We downloaded the expression profiles from the Gene Expression Omnibus (GEO) database. The novel method of single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) was applied to identify immune-related genes and verified in vitro and in vivo experiments. The spared nerve injury (SNI) group was closely related to type1 T helper cells (Th1 cells), and two key genes (Abca1 and Fyb) positively correlated with Th1 cell infiltration. At the single-cell level, Abca1 and Fyb were significantly expressed in macrophages. In addition, we verified that Abca1 could affect the function of macrophages. Finally, we hypothesized that Abca1 is involved in the infiltration of Th1 cells into dorsal root ganglion (DRG) tissues and induces NP via immunoinflammatory response. Hence, the present study aimed to elucidate the correlation between NP and neuroinflammation and identify a new therapeutic target for treating NP.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"19"},"PeriodicalIF":5.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9564834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated endothelial cell markers in systemic lupus erythematosus: a systematic review and meta-analysis.","authors":"S C Bergkamp,&nbsp;M J Wahadat,&nbsp;A Salah,&nbsp;T W Kuijpers,&nbsp;V Smith,&nbsp;S W Tas,&nbsp;J M van den Berg,&nbsp;S Kamphuis,&nbsp;D Schonenberg-Meinema","doi":"10.1186/s12950-023-00342-1","DOIUrl":"https://doi.org/10.1186/s12950-023-00342-1","url":null,"abstract":"<p><strong>Objectives: </strong>To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE.</p><p><strong>Methods: </strong>Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman's rank or Pearson's) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used.</p><p><strong>Results: </strong>From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin.</p><p><strong>Conclusions: </strong>We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"18"},"PeriodicalIF":5.1,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps in acute coronary syndrome.","authors":"Yawen Wu,&nbsp;Shilin Wei,&nbsp;Xiangyang Wu,&nbsp;Yongnan Li,&nbsp;Xue Han","doi":"10.1186/s12950-023-00344-z","DOIUrl":"https://doi.org/10.1186/s12950-023-00344-z","url":null,"abstract":"<p><p>Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, which can cause heart failure, arrhythmia and even sudden death. It is the major cause of disability and death worldwide. Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils activation and have various biological functions. NETs are closely related to the occurrence and development of ACS and also the subsequent damage after myocardial infarction. The mechanisms are complex and interdependent on various pathways, which require further exploration. This article reviewed the role and mechanism of NETs in ACS, thereby providing a valuable reference for the diagnosis and clinical treatment of ACS.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"17"},"PeriodicalIF":5.1,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role.","authors":"Yinjiaozhi Li, Ruoming Tan, Ranran Li, Rui Tian, Zhaojun Liu, Xiaoli Wang, Erzhen Chen, Tingting Pan, Hongping Qu","doi":"10.1186/s12950-023-00341-2","DOIUrl":"10.1186/s12950-023-00341-2","url":null,"abstract":"<p><strong>Background: </strong>Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored.</p><p><strong>Methods: </strong>Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry.</p><p><strong>Results: </strong>PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1^-/- mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis.</p><p><strong>Conclusion: </strong>In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"16"},"PeriodicalIF":4.4,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First trimester human umbilical cord perivascular cells (HUCPVC) modulate the kynurenine pathway and glutamate neurotransmission in an LPS-induced mouse model of neuroinflammation.","authors":"Fyyaz Siddiqui,&nbsp;Denis Gallagher,&nbsp;Hannah Shuster-Hyman,&nbsp;Lianet Lopez,&nbsp;Andrée Gauthier-Fisher,&nbsp;Clifford L Librach","doi":"10.1186/s12950-023-00340-3","DOIUrl":"https://doi.org/10.1186/s12950-023-00340-3","url":null,"abstract":"<p><strong>Background: </strong>The Kynurenine Pathway (KP) of tryptophan degradation and glutamate toxicity is implicated in several neurological disorders, including depression. The therapeutic potential of mesenchymal stromal cells (MSC), owing to their well documented phagocytosis-driven mechanism of immunomodulation and neuroprotection, has been tested in many neurological disorders. However, their potential to influence KP and the glutamatergic system has not yet been investigated. Hence, this study sought to investigate the effect of HUCPVC, a rich and potent source of MSC, on Lipopolysaccharide (LPS)-activated KP metabolites, KP enzymes, and key components of glutamate neurotransmission.</p><p><strong>Methods: </strong>The immunomodulatory effect of peripherally administered HUCPVC on the expression profile of kynurenine pathway metabolites and enzymes was assessed in the plasma and brain of mice treated with LPS using LCMS and QPCR. An assessment of the glutamatergic system, including selected receptors, transporters and related proteins was also conducted by QPCR, immunohistochemistry and Western blot.</p><p><strong>Results: </strong>HUCPVC were found to modulate LPS-induced activation of KP enzymes and metabolites in the brain associated with neurotoxicity. Moreover, the reduced expression of the glutamatergic components due to LPS was also found to be significantly improved by HUCPVC.</p><p><strong>Conclusions: </strong>The immunomodulatory properties of HUCPVC appear to confer neuroprotection, at least in part, through their ability to modulate the KP in the brain. This KP modulation enhances neuroprotective regulators and downregulates neurotoxic consequences, including glutamate neurotoxicity, which is associated with neuroinflammation and depressive behavior.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"15"},"PeriodicalIF":5.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10152638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dioscin alleviates the progression of osteoarthritis: an in vitro and in vivo study.","authors":"Qing Ding,&nbsp;Ruizhuo Zhang,&nbsp;Gaohong Sheng,&nbsp;Tianqi Wang,&nbsp;Shaoze Jing,&nbsp;Tian Ma,&nbsp;Shanxi Wang,&nbsp;Hongqi Zhao,&nbsp;Hua Wu,&nbsp;Wenkai Li","doi":"10.1186/s12950-023-00339-w","DOIUrl":"https://doi.org/10.1186/s12950-023-00339-w","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common joint disease and is the main cause of physical disability in the elderly. Currently, there is no adequate therapeutic strategy to reverse the progression of OA. Many natural plant extracts have received attention in the treatment of OA due to their potential anti-inflammatory properties, and reduced incidence of adverse events. Dioscin (Dio), a natural steroid saponin, has been demonstrated to inhibit the release of inflammatory cytokines in mouse and rat models of various diseases, and has a protective effect in chronic inflammatory diseases. However, whether Dio alleviates OA progression remains to be explored. In this research, our purposes were to investigate the therapeutic potential of Dio in OA. The results demonstrated that Dio exerted anti-inflammatory effects by repressing NO, PGE₂, iNOS and COX-2. Moreover, the application of Dio could repress IL-1β-induced overexpression of matrix metalloproteinases (MMPs, including MMP1, MMP3, and MMP13) and ADAMTS-5, and improve the synthesis of collagen II and aggrecan, which contribute to the maintenance of chondrocyte matrix homeostasis. The underlying mechanism involved the inhibition of the MAPK and NF-κB signaling pathways by Dio. Furthermore, the treatment of Dio significantly improved the pain behaviors of rat OA models. The in vivo study revealed that Dio could ameliorate cartilage erosion and degradation. These results collectively indicate that Dio can be used as a promising and effective agent for the therapy of OA.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"14"},"PeriodicalIF":5.1,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9311773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of CU06-1004 via regulation of inflammation and endothelial permeability in LPS-induced acute lung injury.","authors":"Yeomyeong Kim,&nbsp;Cho-Rong Bae,&nbsp;Dongyeop Kim,&nbsp;Hyejeong Kim,&nbsp;Sunghye Lee,&nbsp;Haiying Zhang,&nbsp;Minyoung Noh,&nbsp;Young-Myeong Kim,&nbsp;Naoki Mochizuki,&nbsp;Young-Guen Kwon","doi":"10.1186/s12950-023-00338-x","DOIUrl":"https://doi.org/10.1186/s12950-023-00338-x","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is a life-threatening condition that fundamentally results from inflammation and edema in the lung. There are no effective treatments available for clinical use. Previously, we found that as a leakage blocker CU06-1004 prevents endothelial barrier disruption and enhances endothelial cell survival under inflammatory conditions. In this study, we aimed to elucidate the effect of CU06-1004 in terms of prevention of inflammation and endothelial dysfunction in an ALI mouse model.</p><p><strong>Methods: </strong>An ALI model was established that included intraperitoneal administration of LPS. Following LPS administration, survival rates and lung wet/dry ratios were assessed. Histological analysis was performed using hematoxylin and eosin staining. Scanning electron microscopy was used to examine alveolar and capillary morphology. Cytokines such as IL-1β, IL-6, and TNF-α were analyzed using an ELISA assay of bronchoalveolar lavage fluid (BALF) and serum. Neutrophil infiltration was observed in BALF using Wright-Giemsa staining, and myeloperoxidase (MPO) activity was assessed. Pulmonary vascular leakage was confirmed using Evans-blue dye, and the expression of junctional proteins was evaluated using immunofluorescent staining. Expression of adhesion molecules was observed using immunofluorescence staining. NF-κB activation was determined using immunohistochemistry and western blot analysis.</p><p><strong>Results: </strong>Survival rates and pulmonary edema were ameliorated with CU06-1004 treatment. Administration of CU06-1004 normalized histopathological changes induced by LPS, and alveolar-capillary wall thickening was reduced. Compared with the LPS-challenged group, after CU06-1004 treatment, the infiltration of immune cells was decreased in the BALF, and MPO activity in lung tissue was reduced. Similarly, in the CU06-1004 treatment group, pro-inflammatory cytokines were significantly inhibited in both BALF and serum. Evans-blue leakage was reduced, and the expression of junctional proteins was recovered in the CU06-1004 group. Adhesion molecules were downregulated and NF-κB activation was inhibited after CU06-1004 treatment.</p><p><strong>Conclusions: </strong>These results suggested that CU06-1004 had a therapeutic effect against LPS-induced ALI via alleviation of the inflammatory response and protection of vascular integrity.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"13"},"PeriodicalIF":5.1,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9275907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network analyses reveal new insights into the effect of multicomponent Tr14 compared to single-component diclofenac in an acute inflammation model.","authors":"Matti Hoch,&nbsp;Suchi Smita,&nbsp;Konstantin Cesnulevicius,&nbsp;Myron Schultz,&nbsp;David Lescheid,&nbsp;Olaf Wolkenhauer,&nbsp;Shailendra Gupta","doi":"10.1186/s12950-023-00335-0","DOIUrl":"https://doi.org/10.1186/s12950-023-00335-0","url":null,"abstract":"<p><strong>Background: </strong>Modifying the acute inflammatory response has wide clinical benefits. Current options include non-steroidal anti-inflammatory drugs (NSAIDs) and therapies that may resolve inflammation. Acute inflammation involves multiple cell types and various processes. We, therefore, investigated whether an immunomodulatory drug that acts simultaneously at multiple sites shows greater potential to resolve acute inflammation more effectively and with fewer side effects than a common anti-inflammatory drug developed as a small molecule for a single target. In this work, we used time-series gene expression profiles from a wound healing mouse model to compare the effects of Traumeel (Tr14), a multicomponent natural product, to diclofenac, a single component NSAID on inflammation resolution.</p><p><strong>Results: </strong>We advance previous studies by mapping the data onto the \"Atlas of Inflammation Resolution\", followed by in silico simulations and network analysis. We found that Tr14 acts primarily on the late phase of acute inflammation (during resolution) compared to diclofenac, which suppresses acute inflammation immediately after injury.</p><p><strong>Conclusions: </strong>Our results provide new insights how network pharmacology of multicomponent drugs may support inflammation resolution in inflammatory conditions.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"12"},"PeriodicalIF":5.1,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9202468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance.","authors":"Gaetano Scaramuzzo, Francesco Nucera, Alessio Asmundo, Roberto Messina, Matilde Mari, Federica Montanaro, Matt D Johansen, Francesco Monaco, Guido Fadda, Giovanni Tuccari, Nicole G Hansbro, Philip M Hansbro, Trevor T Hansel, Ian M Adcock, Antonio David, Paul Kirkham, Gaetano Caramori, Carlo Alberto Volta, Savino Spadaro","doi":"10.1186/s12950-023-00333-2","DOIUrl":"10.1186/s12950-023-00333-2","url":null,"abstract":"<p><p>The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic or cause a disease (COVID-19) characterized by different levels of severity. The main cause of severe COVID-19 and death is represented by acute (or acute on chronic) respiratory failure and acute respiratory distress syndrome (ARDS), often requiring hospital admission and ventilator support.The molecular pathogenesis of COVID-19-related ARDS (by now termed c-ARDS) is still poorly understood. In this review we will discuss the genetic susceptibility to COVID-19, the pathogenesis and the local and systemic biomarkers correlated with c-ARDS and the therapeutic options that target the cell signalling pathways of c-ARDS.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"11"},"PeriodicalIF":4.4,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10027286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9161550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory activity of non-selective PDE inhibitor aminophylline on the lung tissue and respiratory parameters in animal model of ARDS.","authors":"Petra Kosutova,&nbsp;Pavol Mikolka,&nbsp;Daniela Mokra,&nbsp;Andrea Calkovska","doi":"10.1186/s12950-023-00337-y","DOIUrl":"https://doi.org/10.1186/s12950-023-00337-y","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a common complication of critical illness characterized by lung inflammation, epithelial and endothelial dysfunction, alveolar-capillary leakage, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory effects of non-selective phosphodiesterase (PDE) inhibitor aminophylline. New Zealand white rabbits were randomly divided into 3 groups: animals with respiratory failure defined as PaO₂/FiO₂ ratio (P/F) below < 26.7 kPa, and induced by saline lung lavage (ARDS), animals with ARDS treated with intravenous aminophylline (1 mg/kg; ARDS/AMINO), and healthy ventilated controls (Control). All animals were oxygen ventilated for an additional 4 h and respiratory parameters were recorded regularly. Post mortem, the lung tissue was evaluated for oedema formation, markers of inflammation (tumor necrosis factor, TNFα, interleukin (IL)-1β, -6, -8, -10, -13, -18), markers of epithelial damage (receptor for advanced glycation end products, RAGE) and endothelial injury (sphingosine 1-phosphate, S1P), oxidative damage (thiobarbituric acid reactive substances, TBARS, 3-nitrotyrosine, 3NT, total antioxidant capacity, TAC). Aminophylline therapy decreased the levels of pro-inflammatory cytokines, markers of epithelial and endothelial injury, oxidative modifications in lung tissue, reduced lung oedema, and improved lung function parameters compared to untreated ARDS animals. In conclusion, non-selective PDE inhibitor aminophylline showed a significant anti-inflammatory activity suggesting a potential of this drug to be a valuable component of ARDS therapy.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"10"},"PeriodicalIF":5.1,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9127335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}