Inflammation Research最新文献

{"title":"Lazy neutrophils - a lack of DGAT1 reduces the chemotactic activity of mouse neutrophils.","authors":"Alicja Uchańska, Agnieszka Morytko, Kamila Kwiecień, Ewa Oleszycka, Beata Grygier, Joanna Cichy, Patrycja Kwiecińska","doi":"10.1007/s00011-024-01920-6","DOIUrl":"10.1007/s00011-024-01920-6","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils are key players in the innate immune system, actively migrating to sites of inflammation in the highly energetic process of chemotaxis. In this study, we focus on the role of acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the synthesis of triglycerides, the major form of stored energy, in neutrophil chemotaxis.</p><p><strong>Methods and results: </strong>Using a mouse model of psoriasis, we show that DGAT1-deficiency reduces energy-demanding neutrophil infiltration to the site of inflammation, but this inhibition is not caused by decreased glycolysis and reduced ATP production by neutrophils lacking DGAT1. Flow cytometry and immunohistochemistry analysis demonstrate that DGAT1 also does not influence lipid accumulation in lipid droplets during inflammation. Interestingly, as has been shown previously, a lack of DGAT1 leads to an increase in the concentration of retinoic acid, and here, using real-time PCR and publicly-available next-generation RNA sequencing datasets, we show the upregulation of retinoic acid-responsive genes in Dgat1KO neutrophils. Furthermore, supplementation of WT neutrophils with exogenous retinoic acid mimics DGAT1-deficiency in the inhibition of neutrophil chemotaxis in in vitro transwell assay.</p><p><strong>Conclusions: </strong>These results suggest that impaired skin infiltration by neutrophils in Dgat1KO mice is a result of the inhibitory action of an increased concentration of retinoic acid, rather than impaired lipid metabolism in DGAT1-deficient mice.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1631-1643"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751629","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":"Rosiglitazone attenuates Acute Kidney Injury from hepatic ischemia-reperfusion in mice by inhibiting arachidonic acid metabolism through the PPAR-γ/NF-κB pathway.","authors":"Xiaoyan Qin, Zhengli Tan, Qi Li, Shiyi Zhang, Dingheng Hu, Denghui Wang, Liangxu Wang, Baoyong Zhou, Rui Liao, Zhongjun Wu, Yanyao Liu","doi":"10.1007/s00011-024-01929-x","DOIUrl":"10.1007/s00011-024-01929-x","url":null,"abstract":"<p><strong>Background: </strong>Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients.</p><p><strong>Methods: </strong>An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin-eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo.</p><p><strong>Results: </strong>According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein-Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo.</p><p><strong>Conclusions: </strong>These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1765-1780"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DGA ameliorates severe acute pancreatitis through modulating macrophage pyroptosis.","authors":"Xiyue Yue, Lunmeng Lai, Ruina Wang, Lulu Tan, Yanping Wang, Qing Xie, Yunsen Li","doi":"10.1007/s00011-024-01931-3","DOIUrl":"10.1007/s00011-024-01931-3","url":null,"abstract":"<p><p>Severe acute pancreatitis (SAP) is an inflammatory disease with varying severity, ranging from mild local inflammation to severe systemic disease, with a high incidence rate and mortality. Current drug treatments are not ideal. Therefore, safer and more effective therapeutic drugs are urgently needed. 7α,14β-dihydroxy-ent-kaur-17-dimethylamino-3,15-dione DGA, a diterpenoid compound derivatized from glaucocalyxin A, exhibits anti-inflammatory activity. In this study, we demonstrated the therapeutic potential of DGA against SAP and elucidated the underlying mechanisms. Treatment with DGA markedly (1) inhibited death of RAW264.7 and J774a.1 cells induced by Nigericin and lipopolysaccharide, (2) alleviated edema, acinar cell vacuolation, necrosis, and inflammatory cell infiltration of pancreatic tissue in mice, and (3) inhibited the activity of serum lipase and the secretion of inflammatory factor IL-1β. DGA significantly reduced the protein expression of IL-1β and NLRP3 and inhibited the phosphorylation of NF-κB. However, DGA exhibited no inhibitory effect on the expression of caspase-1, gasdermin D (GSDMD), NF-κB, TNF-α, or apoptosis-associated speck-like protein (ASC) and on the cleavage of caspase-1 or GSDMD. Molecular docking simulation confirmed that DGA can bind to TLR4 and IL-1 receptor. In conclusion, DGA may effectively alleviate the symptoms of SAP in mice and macrophages by inhibiting the binding of TLR4 and IL-1 receptor to their ligands; therefore, DGA is a promising drug candidate for the treatment of patients with SAP.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1803-1817"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corynoline alleviates hepatic ischemia–reperfusion injury by inhibiting NLRP3 inflammasome activation through enhancing Nrf2/HO-1 signaling","authors":"Xin Ge, Yue Gu, Wendong Wang, Wenzhi Guo, Panliang Wang, Peng Du","doi":"10.1007/s00011-024-01949-7","DOIUrl":"https://doi.org/10.1007/s00011-024-01949-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Corynoline has displayed pharmacological effects in reducing oxidative stress and inflammatory responses in many disorders. However, its effects on hepatic ischemia–reperfusion (I/R) injury remain unclear. This study aimed to investigate the protective effects of corynoline against hepatic I/R injury and the underlying mechanisms.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Rat models with hepatic I/R injury and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult were constructed. Models were pretreated with corynoline and/or other inhibitors for functional and mechanistic examination.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Corynoline pretreatment effectively mitigated hepatic I/R injury verified by reduced serum transaminase levels, improved histological damage scores, and decreased apoptosis rates. Additionally, corynoline pretreatment significantly inhibited I/R-triggered oxidative stress and inflammatory responses, as indicated by enhanced mitochondrial function, reduced levels of ROS and MDA, reduced neutrophil infiltration and suppressed proinflammatory cytokine release. In vitro experiments further showed that corynoline pretreatment increased cellular viability, decreased LDH activity, reduced cellular apoptosis, and inhibited oxidative stress and inflammatory injury in H/R-induced BRL-3A cells. Mechanistically, corynoline significantly increased Nrf2 nuclear translocation and expression levels of its target gene, HO-1. It also blocked NLRP3 inflammasome activation both in vivo and in vitro. Furthermore, pretreatment with Nrf2 inhibitor ML-385 counteracted the protective effect of corynoline on hepatic I/R injury. Ultimately, in vitro studies revealed that the NLRP3 activator nigericin could also nullified the protective effects of corynoline in BRL-3A cells, but had minimal impact on Nrf2 nuclear translocation.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Corynoline can exert protective effects against hepatic I/R injury by inhibiting oxidative stress, inflammatory responses, and apoptosis. These effects may be associated with inhibiting ROS-induced NLRP3 inflammasome activation by enhancing Nrf2/HO-1 signaling. These data provide new understanding about the mechanism of corynoline action, suggesting it is a potential drug applied for the treatment and prevention of hepatic I/R injury.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"64 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective role of RACK1 in hepatic ischemia‒reperfusion injury-induced ferroptosis","authors":"Zelong Yang, Wenjie Gao, Kai Yang, Weigang Chen, Yong Chen","doi":"10.1007/s00011-024-01944-y","DOIUrl":"https://doi.org/10.1007/s00011-024-01944-y","url":null,"abstract":"<p>Although ferroptosis plays a crucial role in hepatic ischemia‒reperfusion injury (IRI), the molecular mechanisms underlying this process remain unclear. We aimed to explore the potential involvement of the receptor for activated C kinase 1 (RACK1) in hepatic IRI-triggered ferroptosis. Using hepatocyte-specific RACK1 knockout mice and alpha mouse liver 12 (AML12) cells, we conducted a series of in vivo and in vitro experiments. We found that RACK1 has a protective effect on hepatic IRI-induced ferroptosis. Specifically, RACK1 was found to interact with AMPKα through its 1–93 amino acid (aa) region, which facilitates the phosphorylation of AMPKα at threonine 172 (Thr172), ultimately exerting an antiferroptotic effect. Furthermore, the long noncoding RNA (lncRNA) ZNFX1 Antisense 1 (ZFAS1) directly binds to aa 181–317 of RACK1. ZFAS1 has a dual impact on RACK1 by promoting its ubiquitin‒proteasome-mediated degradation and inhibiting its expression at the transcriptional level, which indirectly exacerbates hepatic IRI-induced ferroptosis. These findings underscore the protective role of RACK1 in hepatic IRI-induced ferroptosis and showcase its potential as a prophylactic target for hepatic IRI mitigation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"31 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin-(1–7) decreases inflammation and lung damage caused by betacoronavirus infection in mice","authors":"Erick Bryan de Sousa Lima, Antônio Felipe S. Carvalho, Isabella Zaidan, Adelson Héric A. Monteiro, Camila Cardoso, Edvaldo S. Lara, Fernanda S. Carneiro, Leonardo C. Oliveira, Filipe Resende, Felipe Rocha da Silva Santos, Luiz Pedro Souza-Costa, Ian de Meira Chaves, Celso M. Queiroz-Junior, Remo C. Russo, Robson A. S. Santos, Luciana P. Tavares, Mauro M. Teixeira, Vivian V. Costa, Lirlândia P. Sousa","doi":"10.1007/s00011-024-01948-8","DOIUrl":"https://doi.org/10.1007/s00011-024-01948-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Pro-resolving molecules, including the peptide Angiotensin-(1–7) [Ang-(1–7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1–7) in betacoronavirus infection in mice.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1–7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1–7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Ang-(1–7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1–7) during MHV infection. Ang-(1–7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1–7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Ang-(1–7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"53 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneously blocking ANGPTL3 and IL-1β for the treatment of atherosclerosis through lipid-lowering and anti-inflammation","authors":"Hanqi Wang, Xiaozhi Hu, Yuting Zhang, An Zhu, Jiajun Fan, Zhengyu Wu, Xuebin Wang, Wei Hu, Dianwen Ju","doi":"10.1007/s00011-024-01941-1","DOIUrl":"https://doi.org/10.1007/s00011-024-01941-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Blood lipid levels play a critical role in the progression of atherosclerosis. However, even with adequate lipid reduction, significant residual cardiovascular risk remains. Therefore, it is necessary to seek novel therapeutic strategies for atherosclerosis that can not only lower lipid levels but also inhibit inflammation simultaneously.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The fusion protein FD03-IL-1Ra was designed by linking the Angiopoietin-like 3 (ANGPTL3) nanobody and human interleukin-1 receptor antagonist (IL-1Ra) sequences to a mutated human immunoglobulin gamma 1 (IgG1) Fc. This construct was transfected into HEK293 cells for expression. The purity and thermal stability of the fusion protein were assessed using SDS-PAGE, SEC-HPLC, and differential scanning calorimetry. Binding affinities of the fusion protein to ANGPTL3 and IL-1 receptor were measured using Biacore T200. The biological activity of the fusion protein was validated through in vitro experiments. The therapeutic efficacy of the fusion protein was evaluated in an ApoE-/- mouse model of atherosclerosis, including serum lipid level determination, histological analysis of aorta and aortic sinus sections, and detection of inflammatory and oxidative stress markers. ImageJ software was utilized for quantitative image analysis. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post hoc test.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The FD03-IL-1Ra fusion protein was successfully expressed, with no polymer formation detected, and it demonstrated good thermal and conformational stability. High affinity for both murine and human ANGPTL3 was exhibited by FD03-IL-1Ra, and it was able to antagonize hANGPTL3's inhibition of LPL activity. FD03-IL-1Ra also showed high affinity for both murine and human IL-1R, inhibiting IL-6 expression in A549 cells induced by IL-1β stimulation, as well as suppressing IL-1β-induced activity inhibition in A375.S2 cells. Our study revealed that the fusion protein effectively lowered serum lipid levels and alleviated inflammatory responses in mice. Furthermore, the fusion protein enhanced plaque stability by increasing collagen content within atherosclerotic plaques.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These findings highlighted the potential of bifunctional interleukin-1 receptor antagonist and ANGPTL3 antibody fusion proteins for ameliorating the progression of atherosclerosis, presenting a promising novel therapeutic approach targeting both inflammation and lipid levels.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"26 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinin B1 receptor deficiency promotes enhanced adipose tissue thermogenic response to β3-adrenergic stimulation.","authors":"Jéssica Branquinho, Raquel L Neves, Renan P Martin, Júlia G Arata, Clarissa A Bittencourt, Ronaldo C Araújo, Marcelo Y Icimoto, João B Pesquero","doi":"10.1007/s00011-024-01917-1","DOIUrl":"10.1007/s00011-024-01917-1","url":null,"abstract":"<p><strong>Objective and design: </strong>Kinin B1 receptor (B1R) has a key role in adipocytes to protect against obesity and glycemic metabolism, thus becoming a potential target for regulation of energy metabolism and adipose tissue thermogenesis.</p><p><strong>Material or subjects: </strong>Kinin B1 knockout mice (B1KO) were subjected to acute induction with CL 316,243 and chronic cold exposure.</p><p><strong>Methods: </strong>Metabolic and histological analyses, gene and protein expression and RNA-seq were performed on interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of mice.</p><p><strong>Results: </strong>B1KO mice, under acute effect of CL 316,243, exhibited increased energy expenditure and upregulated thermogenic genes in iWAT. They were also protected from chronic cold, showing enhanced non-shivering thermogenesis with increased iBAT mass (~ 90%) and recruitment of beige adipocytes in iWAT (~ 50%). Positive modulation of thermogenic and electron transport chain genes, reaching a 14.5-fold increase for Ucp1 in iWAT. RNA-seq revealed activation of the insulin signaling pathways for iBAT and oxidative phosphorylation, tricarboxylic acid cycle, and browning pathways for iWAT.</p><p><strong>Conclusion: </strong>B1R deficiency induced metabolic and gene expression alterations in adipose tissue, activating thermogenic pathways and increasing energy metabolism. B1R antagonists emerge as promising therapeutic targets for regulating obesity and associated metabolic disorders, such as inflammation and diabetes.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1565-1579"},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor receptor 4 deficiency in macrophages aggravates experimental colitis by promoting M1-polarization.","authors":"Luyao Shen, Cong Wang, Ran Ren, Xudong Liu, Dongqin Zhou, Yu Chen, Yu Zhou, Juan Lei, Yang Xiao, Nan Zhang, Huakan Zhao, Yongsheng Li","doi":"10.1007/s00011-024-01910-8","DOIUrl":"10.1007/s00011-024-01910-8","url":null,"abstract":"<p><strong>Objective and design: </strong>Compelling evidence indicates that dysregulated macrophages may play a key role in driving inflammation in inflammatory bowel disease (IBD). Fibroblast growth factor (FGF)-19, which is secreted by ileal enterocytes in response to bile acids, has been found to be significantly lower in IBD patients compared to healthy individuals, and is negatively correlated with the severity of diarrhea. This study aims to explore the potential impact of FGF19 signaling on macrophage polarization and its involvement in the pathogenesis of IBD.</p><p><strong>Methods: </strong>The dextran sulfate sodium (DSS)-induced mouse colitis model was utilized to replicate the pathology of human IBD. Mice were created with a conditional knockout of FGFR4 (a specific receptor of FGF19) in myeloid cells, as well as mice that overexpressing FGF19 specifically in the liver. The severity of colitis was measured using the disease activity index (DAI) and histopathological staining. Various techniques such as Western Blotting, quantitative PCR, flow cytometry, and ELISA were employed to assess polarization and the expression of inflammatory genes.</p><p><strong>Results: </strong>Myeloid-specific FGFR4 deficiency exacerbated colitis in the DSS mouse model. Deletion or inhibition of FGFR4 in bone marrow-derived macrophages (BMDMs) skewed macrophages towards M1 polarization. Analysis of transcriptome sequencing data revealed that FGFR4 deletion in macrophages significantly increased the activity of the complement pathway, leading to an enhanced inflammatory response triggered by LPS. Mechanistically, FGFR4-knockout in macrophages promoted complement activation and inflammatory response by upregulating the nuclear factor-κB (NF-κB)-pentraxin3 (PTX3) pathway. Additionally, FGF19 suppressed these pathways and reduced inflammatory response by activating FGFR4 in inflammatory macrophages. Liver-specific overexpression of FGF19 also mitigated inflammatory responses induced by DSS in vivo.</p><p><strong>Conclusion: </strong>Our study highlights the significance of FGF19-FGFR4 signaling in macrophage polarization and the pathogenesis of IBD, offering a potential new therapeutic target for IBD.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1493-1510"},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of monoclonal antibodies targeting TSLP and IgE in asthma management.","authors":"Shuang Yan, Bowen Yang, Haichuan Qin, Chengzhen Du, Hua Liu, Tengchuan Jin","doi":"10.1007/s00011-024-01908-2","DOIUrl":"10.1007/s00011-024-01908-2","url":null,"abstract":"<p><strong>Background: </strong>In recent years, there has been a growing interest in the utilization of biologic therapies for the management of asthma. Both TSLP and IgE are important immune molecules in the development of asthma, and they are involved in the occurrence and regulation of inflammatory response.</p><p><strong>Methods: </strong>A comprehensive search of PubMed and Web of Science was conducted to gather information on anti-TSLP antibody and anti-IgE antibody.</p><p><strong>Results: </strong>This investigation elucidates the distinct mechanistic roles of Thymic Stromal Lymphopoietin (TSLP) and Immunoglobulin E (IgE) in the pathogenesis of asthma, with a particular emphasis on delineating the therapeutic mechanisms and pharmacological properties of monoclonal antibodies targeting IgE and TSLP. Through a meticulous examination of clinical trials involving paradigmatic agents such as omalizumab and tezepelumab, we offer valuable insights into the potential treatment modalities for diseases with shared immunopathogenic pathways involving IgE and TSLP.</p><p><strong>Conclusion: </strong>The overarching objective of this comprehensive study is to delve into the latest advancements in asthma therapeutics and to provide guidance for future investigations in this domain.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1425-1434"},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}