Journal of Inflammation-London最新文献

{"title":"The effects of chronic, continuous β-funaltrexamine pre-treatment on lipopolysaccharide-induced inflammation and behavioral deficits in C57BL/6J mice.","authors":"Karissa Hodge, Daniel J Buck, Subhas Das, Randall L Davis","doi":"10.1186/s12950-024-00407-9","DOIUrl":"10.1186/s12950-024-00407-9","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and neuroinflammation are integral to the progression and severity of many diseases and are strongly associated with cardiovascular disease, cancer, autoimmune disorders, neurodegenerative disease, and neuropsychiatric disorders. These diseases can be difficult to treat without addressing the underlying inflammation, and, as such, a growing need has arisen for pharmaceutical treatments that target inflammatory mediators and signaling pathways. Our lab has investigated the therapeutic potential of the irreversible µ-opioid antagonist β-funaltrexamine (β-FNA) and discovered that acute treatment ameliorates inflammation in astrocytes in vitro and inhibits central and peripheral inflammation and reduces anxiety- and sickness-like behavior in male C57BL/6J mice. Now, our investigation has expanded to investigate the chronic pre-treatment effects of β-FNA on lipopolysaccharide (LPS)-induced inflammation and behavior in male C57BL/6J mice.</p><p><strong>Results: </strong>Micro-osmotic drug pumps were surgically inserted into the subcutaneous intrascapular space of male C57BL/6J mice. β-FNA or saline vehicle was continuously administered for seven days. On the sixth day, mice were given intraperitoneal injections of LPS or saline. An elevated plus maze test, followed by a forced swim test, were administered 24 h post-injection to measure sickness-, anxiety- and depressive-like behavior. Immediately after testing, frontal cortex, hippocampus, spleen, and plasma were collected. Levels of inflammatory chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) were measured in tissues by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to assess expression of the enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) and the NLR family pyrin domain-containing protein 3 (NRLP3) inflammasome in frontal cortex and spleen tissues. Chronic pre-treatment robustly decreased inflammation in the hippocampus, frontal cortex, and spleen and reduced or abolished anxiety- and sickness-like behavior (e.g., increased time spent motionless, increased time spent in a contracted position, and reduced distance moved). However, treatment with β-FNA alone increased both inflammation in the frontal cortex and anxiety-like behavior.</p><p><strong>Conclusion: </strong>These findings provide novel insights into the anti-inflammatory and behavior-modifying effects of chronic β-FNA pre-treatment and continue to support the therapeutic potential of β-FNA under inflammatory conditions.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"33"},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121152","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":"Mulberroside A mitigates intervertebral disc degeneration by inhibiting MAPK and modulating Ppar-γ/NF-κB pathways.","authors":"Tao Xu, Hongqi Zhao, Xuan Fang, Shanxi Wang, Jian Li, Hua Wu, Weihua Hu, Rui Lu","doi":"10.1186/s12950-024-00398-7","DOIUrl":"10.1186/s12950-024-00398-7","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in many diseases. Whereas, there is little exploration of the therapeutic potential of MA on IVDD. This study aimed at the therapeutic potential of MA on IVDD in vivo and in vitro and the mechanism involved.</p><p><strong>Methods: </strong>In vitro, western blotting, RT-qPCR, and immunofluorescence analysis were implemented to explore the bioactivity of MA on interleukin-1 beta (IL-1β)-induced inflammation nucleus pulposus cells (NPCs) isolated from Sprague-Dawley male rats. In vivo, X-ray and MRI were applied to measure the morphological changes, and histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disc sections on puncture-induced IVDD rat models.</p><p><strong>Results: </strong>In vitro, MA up-regulated the expression level of anabolic-related proteins (Aggrecan and Collagen II) and decreased catabolic-related proteins (Mmp2, Mmp3, Mmp9, and Mmp13) in IL-1β-induced NPCs. Furthermore, MA inhibits the production of pro-inflammatory factors (Inos, Cox-2, and Il-6) stimulated by IL-1β. Mechanistically, MA inhibited the signal transduction of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways in IL-1β-induced NPCs. Moreover, MA might bind to Ppar-γ and then suppress the NF-kB pathway. In vivo experiment illustrated that MA mitigates the IVDD progression in puncture-induced IVDD model. X-ray and MRI images showed MA restore the disc height and T2-weighted signal intensity after puncturing. H&E and Safranin O/Fast Green also showed MA also alleviated morphological changes caused by acupuncture. In addition, MA reversed the expression level of Mmp13, Aggrecan, Collagen II, and Ppar-γ induced in IVDD models.</p><p><strong>Conclusions: </strong>MA inhibited degenerative phenotypes in NPCs and alleviated IVDD progression via inhibiting the MAPK and NF-κB pathways; besides, MA suppressed the NF-κB pathway was attributed to activating Ppar-γ, those supported that MA or Ppar-γ might be a potential drug or target for IVDD.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"32"},"PeriodicalIF":4.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094250","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":"MicroRNA mediated suppression of airway lactoperoxidase by TGF-β1 and cigarette smoke promotes airway inflammation.","authors":"Maria J Santiago, Srinivasan Chinnapaiyan, Kingshuk Panda, Md Sohanur Rahman, Suvankar Ghorai, Joseph H Lucas, Stephen M Black, Irfan Rahman, Hoshang J Unwalla","doi":"10.1186/s12950-024-00405-x","DOIUrl":"10.1186/s12950-024-00405-x","url":null,"abstract":"<p><p>Transforming Growth Factor Beta1 (TGF-β1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COPD. Chronic inflammation is a hallmark of COPD. However, the underlying mechanisms remain unknown. Previous research has suggested that TGF-β1 alters the airway epithelial microRNAome and transcriptome, potentially contributing to lung inflammation. The Lactoperoxidase (LPO) system is an integral component of innate immunity within the airway. LPO plays a crucial role in host defense by catalyzing the oxidation of thiocyanate to hypothiocyanite in the presence of hydrogen peroxide (H₂O₂), generating a potent antibacterial and antiviral agent. Additionally, the LPO system potentially aids in maintaining cellular redox balance by reducing the levels of H₂O₂, thus mitigating oxidative stress within the airway epithelium. LPO dysfunction can impair immune responses and exacerbate inflammatory processes in respiratory diseases.In this study, primary bronchial epithelial cells and bronchial cell lines were treated with TGF-β1 and exposed to cigarette smoke to characterize the effect of these factors on LPO and their downstream effects. RT-qPCR and Western Blot were applied to quantify mRNA and proteins' expression. The levels of H₂O₂ were detected using the Amplex Red Assay. Magnetofection and transfection were applied to probe the effect of miR-449b-5p. Staining procedures using the MitoTracker Green and C12FDG dyes were used to establish mitochondria mass and senescence. The levels of pro-inflammatory cytokines were measured via Luminex assays.We found that TGF-β1 and cigarette smoke suppressed airway LPO expression, increasing H₂O₂ levels. This increase in H₂O₂ had downstream effects on mitochondrial homeostasis, epithelial cellular senescence, and the pro-inflammatory cytokine response. We demonstrate for the first time that airway LPO is regulated by TGF-β1-induced miRNA-mediated post-transcriptional silencing through miR-449b-5p in the lungs. Further, we identify and validate miR-449-5p as the candidate miRNA upregulated by TGF-β1, which is involved in LPO suppression. This paper demonstrates a new mechanism by which TGF-β1 can lead to altered redox status in the airway.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"31"},"PeriodicalIF":4.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082718","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":"Impairment of Nrf2 signaling in the hippocampus of P301S tauopathy mice model aligns with the cognitive impairment and the associated neuroinflammation.","authors":"Ahmed Sabry Mohamed, Mahmoud ElKaffas, Karim Metwally, Mahmoud Abdelfattah, Eslam Ashraf Elsery, Ahmed Elshazly, Hossam Eldin Gomaa, Aziza Alsayed, Sara El-Desouky, Randa El-Gamal, Sara Elfarrash","doi":"10.1186/s12950-024-00396-9","DOIUrl":"10.1186/s12950-024-00396-9","url":null,"abstract":"<p><p>Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant hyperphoshorylated tau filaments, the associated neuroinflammation and disease phenotype. However, the exact underpinning mechanisms are still not fully addressed that hinder our understanding of the tauopathy diseases and the development of possible therapeutic targets.Methods: In the current study, hippocampus from three disease time points (2, 4 and 6 months) of P301S mice were further characterized in comparison to the age and sex matched control wild type mice (WT) that do not express the transgene. Different spectrum of hippocampal dependent cognitive tests, biochemical and pathological analysis were conducted to understand the disease progression and the associated changes in each stage. Results: Cognitive impairment was manifested as early as 2 months age, prior to the identification of tau aggregation and phosphorylation by immunostaining. P301S mice manifested an increased pro-inflammatory related changes at mRNA transcription level (IL-1b and IL17A) with the progression of the disease and when compared to the WT mice of the same age. Among the identified genes in the current study, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) genes expression that is considered as the master regulator of an endogenous inducible defense system was significantly impaired in P301S mice by 4 and 6 months when compared to healthy WT controls. A data that was also supported by the immunostaining of the serial brain sections including the both brain stem and hippocampus. The current result is suggesting that the downregulation of Nrf2 gene and the impaired Nrf2 dependent anti-inflammatory mechanisms in P301S mice brain is possibly contributing -among other factors- in the neuroinflammation and tauopathy, and that modulation of Nrf2 signaling impairments can be further investigated as a promising potential therapeutic target for tauopathy.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"29"},"PeriodicalIF":4.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899016","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":"Correction: Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.","authors":"Tabata Maruyama Dos Santos, Renato Fraga Righetti, Leandro do Nascimento Camargo, Edna Aparecida Leick, Silvia Fukuzaki, Elaine Cristina de Campos, Thiago Tafarel Galli, Beatriz Mangueira Saraiva-Romanholo, Luana Laura Sales da Silva, Jéssica Anastácia Silva Barbosa, Juliana Morelli Lopes Gonçalves João, Carla Máximo Prado, Bianca Goulart de Rezende, Christine Laure Marie Bourotte, Fernanda Degobbi Tenorio Quirino Dos Santos Lopes, Milton de Arruda Martins, Isabela M Bensenor, João Vitor de Oliveira Cirillo, Suellen Karoline Moreira Bezerra, Fabio José Alencar Silva, Marcela Souza Lima Paulo, Paulo A Lotufo, Iolanda de Fátima Lopes Calvo Tibério","doi":"10.1186/s12950-024-00401-1","DOIUrl":"10.1186/s12950-024-00401-1","url":null,"abstract":"","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"28"},"PeriodicalIF":4.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857269","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":"MAP3K8 is a potential therapeutic target in airway epithelial inflammation.","authors":"Chih-Yung Chiu, Saffron A G Willis-Owen, Kenny C C Wong, Stuart N Farrow, William O C Cookson, Miriam F Moffatt, Youming Zhang","doi":"10.1186/s12950-024-00400-2","DOIUrl":"10.1186/s12950-024-00400-2","url":null,"abstract":"<p><strong>Background: </strong>We have previously discovered clusters of sequentially negative and positive modulators of acute inflammation during cytokine stimulation in epithelial cells and identified potential targets for therapy within these clusters. MAP3K8 is a druggable kinase that we found to be a hub of a principal interaction network. We describe here the results of MAP3K8 knockdown in the A549 lung cancer cell line, the BEAS-2B epithelial cell line and normal human bronchial epithelial (NHBE) cells following IL-1β stimulation. We analysed signalling transduction and global gene expression after IL-1β stimulation with and without MAP3K8 knockdown, quantifying levels of the inflammatory cytokines IL-6, IL-8 and RANTES levels by qPCRs and/or by ELISAs. We also examined potential small molecule inhibitors for MAP3K8 in the same models.</p><p><strong>Results: </strong>IL-1β significantly and consistently increased MAP3K8 expression after 2 h in A549, BEAS-2B and NHBE cells. Phosphorylation of MAP3K8 occurred at 20 min after IL-1β stimulation and MAP3K8 protein was degraded at 30 min. MAP3K8 knockdown significantly reduced IL-6, IL-8 levels after IL-1β stimulation and yielded a 10-fold enhancement of the anti-inflammatory effects of dexamethasone. Phosphorylation of ERK1/2 (P-ERK1/2) and phosphorylation of SAPK/JNK (P-SAPK/JNK) decreased at 30 min after IL-1β stimulation with MAP3K8 knockdown. The combination of dexamethasone and MAP3K8 knockdown resulted in greater inhibition of phosphorylated ERK1/2 and SAPK/JNK. Nineteen genes including MMP1, MMP3, MMP10, ITGB8, LAMC2 and PLAT (P corrected < 0.01 respectively) demonstrated a distinct altered temporal response to IL-1β following suppression of MAP3K8. However, putative MAP3K8 inhibitors including Tpl2-1, Tpl2-2 and GSK2222867A only showed inhibition of IL-6 and IL-8 production at a high dose.</p><p><strong>Conclusions: </strong>These results confirm that MAP3K8 is a key mediator of the early inflammatory response and that it is a potential target in inflammatory diseases. However, current tool compounds do not effectively inhibit its effects.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"27"},"PeriodicalIF":4.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728334","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":"Emodin alleviates intestinal ischemia-reperfusion injury through antioxidant stress, anti-inflammatory responses and anti-apoptosis effects via Akt-mediated HO-1 upregulation.","authors":"Yinyin Liu, Tuo Ji, Haixing Jiang, Meng Chen, Wanli Liu, Zongze Zhang, Xianghu He","doi":"10.1186/s12950-024-00392-z","DOIUrl":"10.1186/s12950-024-00392-z","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia-reperfusion (I/R) injury is a severe vascular emergency. Previous research indicated the protective effects of Emodin on I/R injury. Our study aims to explore the effect of Emodin on intestinal I/R (II/R) injury and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>C57BL/6 mice and Caco-2 cells were used for in vivo and in vitro studies. We established an animal model of II/R injury by temporarily occluding superior mesenteric artery. We constructed an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model using a hypoxia-reoxygenation incubator. Different doses of Emodin were explored to determine the optimal therapeutic dose. Additionally, inhibitors targeting the protein kinase B (Akt) or Heme oxygenase-1 (HO-1) were administered to investigate their potential protective mechanisms.</p><p><strong>Results: </strong>Our results demonstrated that in animal experiments, Emodin mitigated barrier disruption, minimized inflammation, reduced oxidative stress, and inhibited apoptosis. When Akt or HO-1 was inhibited, the protective effect of Emodin was eliminated. Inhibiting Akt also reduced the level of HO-1. In cell experiments, Emodin reduced inflammation and apoptosis in the OGD/R cell model. Additionally, when Akt or HO-1 was inhibited, the protective effect of Emodin was weakened.</p><p><strong>Conclusions: </strong>Our findings suggest that Emodin may protect the intestine against II/R injury through the Akt/HO-1 signaling pathway.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"25"},"PeriodicalIF":4.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565146","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":"Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach.","authors":"Mohammad Hasan Maleki, Omid Vakili, Ramin Tavakoli, Elham Nadimi, Zahra Noori, Motahareh Taghizadeh, Amirreza Dehghanian, Lobat Tayebi, Sayed Mohammad Shafiee","doi":"10.1186/s12950-024-00397-8","DOIUrl":"10.1186/s12950-024-00397-8","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis.</p><p><strong>Methods: </strong>Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure.</p><p><strong>Results: </strong>Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin.</p><p><strong>Conclusion: </strong>These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"26"},"PeriodicalIF":4.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565196","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":"Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.","authors":"Tabata Maruyama Dos Santos, Renato Fraga Righetti, Leandro do Nascimento Camargo, Edna Aparecida Leick, Silvia Fukuzaki, Elaine Cristina de Campos, Thiago Tafarel Galli, Beatriz Mangueira Saraiva-Romanholo, Luana Laura Sales da Silva, Jéssica Anastácia Silva Barbosa, Juliana Morelli Lopes Gonçalves João, Carla Máximo Prado, Bianca Goulart de Rezende, Christine Laure Marie Bourotte, Fernanda Degobbi Tenorio Quirino Dos Santos Lopes, Milton de Arruda Martins, Isabela M Bensenor, João Vitor de Oliveira Cirillo, Suellen Karoline Moreira Bezerra, Fabio José Alencar Silva, Marcela Souza Lima Paulo, Paulo A Lotufo, Iolanda de Fátima Lopes Calvo Tibério","doi":"10.1186/s12950-024-00399-6","DOIUrl":"10.1186/s12950-024-00399-6","url":null,"abstract":"<p><strong>Introduction: </strong>Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood.</p><p><strong>Methods: </strong>One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system.</p><p><strong>Results: </strong>During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress.</p><p><strong>Conclusions: </strong>Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"24"},"PeriodicalIF":4.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499761","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":"Microcirculatory disturbance in acute liver injury is triggered by IFNγ-CD40 axis.","authors":"Miho Kurokawa, Takeshi Goya, Motoyuki Kohjima, Masatake Tanaka, Sadahiro Iwabuchi, Shigeyuki Shichino, Satoshi Ueha, Tomonobu Hioki, Tomomi Aoyagi, Motoi Takahashi, Koji Imoto, Shigeki Tashiro, Hideo Suzuki, Masaki Kato, Shinichi Hashimoto, Hideo Matsuda, Kouji Matsushima, Yoshihiro Ogawa","doi":"10.1186/s12950-024-00387-w","DOIUrl":"10.1186/s12950-024-00387-w","url":null,"abstract":"<p><strong>Background: </strong>Acute liver failure (ALF) is a life-threatening disorder that progresses from self-limiting acute liver injury (ALI). Microcirculatory disturbance characterized by sinusoidal hypercoagulation and subsequent massive hypoxic hepatocyte damage have been proposed to be the mechanism by which ALI deteriorates to ALF; however, the precise molecular pathway of the sinusoidal hypercoagulation remains unknown. Here, we analyzed ALI patients and mice models to uncover the pathogenesis of ALI with microcirculatory disturbance.</p><p><strong>Methods: </strong>We conducted a single-center retrospective study for ALI and blood samples and liver tissues were analyzed to evaluate the microcirculatory disturbance in ALI patients (n = 120). Single-cell RNA sequencing analysis (scRNA-seq) was applied to the liver from the concanavalin A (Con A)‑induced mouse model of ALI. Interferon-gamma (IFNγ) and tumor necrosis factor-alpha knockout mice, and primary human liver sinusoidal endothelial cells (LSECs) were used to assess the mechanism of microcirculatory disturbance.</p><p><strong>Results: </strong>The serum IFNγ concentrations were significantly higher in ALI patients with microcirculatory disturbance than in patients without microcirculatory disturbance, and the IFNγ was upregulated in the Con A mouse model which presented microcirculatory disturbance. Hepatic IFNγ expression was increased as early as 1 hour after Con A treatment prior to sinusoidal hypercoagulation and hypoxic liver damage. scRNA-seq revealed that IFNγ was upregulated in innate lymphoid cells and stimulated hepatic vascular endothelial cells at the early stage of liver injury. In IFNγ knockout mice treated with Con A, the sinusoidal hypercoagulation and liver damage were remarkably attenuated, concomitant with the complete inhibition of CD40 and tissue factor (TF) upregulation in vascular endothelial cells. By ligand-receptor analysis, CD40-CD40 ligand interaction was identified in vascular endothelial cells. In human LSECs, IFNγ upregulated CD40 expression and TF was further induced by increased CD40-CD40 ligand interaction. Consistent with these findings, hepatic CD40 expression was significantly elevated in human ALI patients with microcirculatory disturbance.</p><p><strong>Conclusion: </strong>We identified the critical role of the IFNγ-CD40 axis as the molecular mechanism of microcirculatory disturbance in ALI. This finding may provide novel insights into the pathogenesis of ALI and potentially contribute to the emergence of new therapeutic strategies for ALI patients.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"21 1","pages":"23"},"PeriodicalIF":4.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437860","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}