Journal of Inflammation-London最新文献

{"title":"LL-37 and citrullinated-LL-37 modulate IL-17A/F-mediated responses and selectively suppress Lipocalin-2 in bronchial epithelial cells.","authors":"Anthony Altieri, Dylan Lloyd, Padmanie Ramotar, Anne M van der Does, Mahadevappa Hemshekhar, Neeloffer Mookherjee","doi":"10.1186/s12950-025-00446-w","DOIUrl":"10.1186/s12950-025-00446-w","url":null,"abstract":"<p><strong>Background: </strong>Levels of the human cationic antimicrobial host defence peptide LL-37 are enhanced in the lungs during neutrophilic airway inflammation. LL-37 drives Th17 differentiation, and Th17 cells produce IL-17A and IL-17F which form the biologically active heterodimer IL-17A/F. While IL-17 is a critical mediator of neutrophilic airway inflammation, LL-37 exhibits contradictory functions; LL-37 can both promote and mitigate neutrophil recruitment depending on the inflammatory milieu. The impact of LL-37 on IL-17-induced responses in the context of airway inflammation remains largely unknown. Therefore, we examined signaling intermediates and downstream responses mediated by the interplay of IL-17A/F and LL-37 in human bronchial epithelial cells (HBEC). As LL-37 can become citrullinated during airway inflammation, we also examined LL-37-mediated downstream responses compared to that with citrullinated LL-37 (citLL-37) in HBEC.</p><p><strong>Results: </strong>Using an aptamer-based proteomics approach, we identified proteins that are altered in response to IL-17A/F in HBEC. Proteins enhanced in response to IL-17A/F were primarily neutrophil chemoattractants, including chemokines and proteins associated with neutrophil migration such as lipocalin-2 (LCN-2). We showed that selective depletion of LCN-2 mitigates neutrophil migration, functionally demonstrating LCN-2 as a critical neutrophil chemoattractant. We further demonstrated that LL-37 and citLL-37 selectively suppress IL-17A/F-induced LCN-2 abundance in HBEC. Mechanistic studies revealed that LL-37 and citLL-37 suppresses IL-17 A/F-mediated enhancement of C/EBPβ, a transcription factor required for LCN-2 production. In contrast, LL-37 and citLL-37 enhance the abundance of ribonuclease Regnase-1, which is a negative regulator of IL-17 and LCN-2 in HBEC. In an animal model of allergen-challenged airway inflammation with elevated IL-17A/F and neutrophil elastase in the lungs, we demonstrated that CRAMP (mouse orthologue of LL-37) negatively correlates with LCN-2.</p><p><strong>Conclusions: </strong>Overall, our findings showed that LL-37 and citLL-37 can selectively suppress the abundance of IL-17A/F-mediated LCN-2, a protein that is critical for neutrophil migration in HBEC. These results suggest that LL-37, and its modified citrullinated form, have the potential to negatively regulate IL-17-mediated neutrophil migration during airway inflammation. To our knowledge, this is the first study to report that the immunomodulatory function of LL-37 enhances the RNA binding protein Regnase-1, suggesting that a post-transcriptional mechanism of action is mediated by the peptide.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"20"},"PeriodicalIF":4.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133340","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":"Exosomes derived from M2 macrophages regulate airway inflammation by modulating epithelial cell proliferation and apoptosis.","authors":"Yinying Ren, Mi Zhou, Yuehan Li, Yan Li, JinYing Xiang, Fang Deng, Zhengxiu Luo, Enmei Liu, Jinyue Yu, Zhou Fu, Fengxia Ding, Bo Liu","doi":"10.1186/s12950-025-00444-y","DOIUrl":"10.1186/s12950-025-00444-y","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic inflammatory disease characterized by airway remodeling and immune dysregulation. This study aimed to explore the mechanisms by which M2 macrophage-derived exosomes (M2Φ-Exos) regulate airway inflammation in asthma by modulating epithelial cell proliferation and apoptosis.</p><p><strong>Methods: </strong>M2Φ-Exos were extracted and characterized by morphology, size, and marker protein expression. In vitro, the effects of M2Φ-Exos on House Dust Mites (HDM)-stimulated mouse lung epithelial cells (MLE-12s) were evaluated using western blotting to analyze Proliferating Cell Nuclear Antigen (PCNA), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 expression. In vivo, M2Φ-Exos were administered to HDM-induced asthmatic mice to assess their impact on airway inflammation, epithelial remodeling, and proliferation-apoptosis balance using immunohistochemistry, immunofluorescence, and western blotting. Cytokine levels in lung tissue and bronchoalveolar lavage fluid (BALF) were measured by qRT-PCR and ELISA.</p><p><strong>Results: </strong>M2Φ-Exos displayed typical cup-shaped morphology, an average diameter of 115.5 nm, and expressed marker proteins CD9, TSG101, and CD63. MLE-12 cells internalized M2Φ-Exos, leading to reduced abnormal proliferation and apoptosis in HDM-stimulated cells. In asthmatic mice, M2Φ-Exos alleviated airway inflammation and epithelial thickening while reducing PCNA, cleaved caspase-3, and Bax levels and increasing Bcl-2 expression. M2Φ-Exos suppressed pro-inflammatory cytokines (IL-4, IL-5, IL-13) and Transforming growth factor (TGF)-β, while enhancing anti-inflammatory cytokine IFN-γ and IL-10.</p><p><strong>Conclusion: </strong>These findings demonstrate that M2Φ-Exos regulate the imbalance in epithelial proliferation and apoptosis in asthma, reducing inflammation and mitigating tissue remodeling, and provide new insights into potential therapeutic strategies for asthma management.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"19"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103331","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":"Exosomal non-coding RNAs: gatekeepers of inflammation in autoimmune disease.","authors":"Mohamed J Saadh, Omer Qutaiba B Allela, Ali Fawzi Al-Hussainy, Lalji Baldaniya, M M Rekha, Deepak Nathiya, Parjinder Kaur, Zafar Aminov, Hayder Naji Sameer, Huda Ghassan Hameed, Zainab H Athab, Mohaned Adil","doi":"10.1186/s12950-025-00443-z","DOIUrl":"https://doi.org/10.1186/s12950-025-00443-z","url":null,"abstract":"<p><p>Autoimmune diseases (AIDs) are marked by systemic inflammation and immune dysregulation, yet current therapies often fail to target their underlying causes. Emerging evidence positions exosomal non-coding RNAs (ncRNAs)-including miRNAs, lncRNAs, and circRNAs-as key regulators of inflammatory pathways, providing critical insights into AID pathogenesis. This review synthesizes recent advances in how these ncRNAs orchestrate immune cell communication, modulate inflammatory mediators, and drive microglial activation in neuroinflammatory AIDs. It evaluates their dual role as disease amplifiers (e.g., miR-155 in lupus, miR-326 in rheumatoid arthritis) and therapeutic targets, emphasizing their potential to reprogram immune responses or deliver anti-inflammatory agents. In this review, we first provide a glimpse into the pathogenesis of autoimmune diseases and delve into the structure and function of exosomes, emphasizing their role in cell-cell communication. We then discuss the regulatory roles of exosomal ncRNAs in immune modulation, detailing their types, functions, and mechanisms of action. Finally, we examine the implications of exosomes and exosomal ncRNAs in the context of autoimmune diseases, with a particular focus on microglial activation and its contribution to neuroinflammation.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"18"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082281","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":"Biological mechanisms and therapeutic prospects of interleukin-33 in pathogenesis and treatment of allergic disease.","authors":"Mohammad Chand Jamali, Asma'a H Mohamed, Azfar Jamal, Mohammad Azhar Kamal, Waleed Al Abdulmonem, Bashar Abdullah Saeed, Nasrin Mansuri, Fuzail Ahmad, Mustafa Mudhafar, Alaa Shafie, Haroonrashid M Hattiwale","doi":"10.1186/s12950-025-00438-w","DOIUrl":"10.1186/s12950-025-00438-w","url":null,"abstract":"<p><p>Allergic diseases significantly impact the quality of life of people around the world. Cytokines play a crucial role in regulating the immune system. Due to their importance in pro-inflammatory mechanisms, cytokines are used to understand pathogenesis and serve as biomarkers in many diseases. One such cytokine is interleukin-33, a member of the IL-1 family, including IL- 1α, IL-1β, and IL-18. The IL-33 receptor is a heterodimer of IL-1 receptor-like 1 and IL-1 receptor accessory protein. IL-33 plays a critical role in regulating innate and adaptive immune responses. The primary targets of IL-33 in vivo are tissue-resident immune cells, including mast cells, group 2 innate lymphoid cells, regulatory T cells, T helper 2 cells, eosinophils, basophils, dendritic cells, Th1 cells, CD8 + T cells, NK cells, iNKT cells, B cells, neutrophils, and macrophages. However, IL-33 appears to act as an alarm signal that is promptly released by producing cells under cellular damage or stress conditions. IL-33 regulates signaling and various biological functions, including induction of pro-inflammatory cytokines, regulation of cell proliferation, and involvement in tissue remodeling. IL-33 is fundamental in immune-related diseases and plays a critical role in the control of inflammation. Recently, IL-33 has been shown to significantly impact allergic diseases, primarily by inducing Th2 immune responses. IL-33 is a key regulator of mast cell function and a promising therapeutic target for treating allergic diseases. This review provides an overview of the current understanding of the role of IL-33 in allergy pathogenesis and potential clinical approaches.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"17"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057449","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":"Comparison of the inflammatory biomarkers IL- 6, TNF-α, and CRP to predict the effect of nutritional therapy on mortality in medical patients at risk of malnutrition : A secondary analysis of the randomized clinical trial EFFORT.","authors":"Carla Wunderle, Elisabeth Martin, Alma Wittig, Pascal Tribolet, Thomas A Lutz, Christina Köster-Hegmann, Zeno Stanga, Beat Mueller, Philipp Schuetz","doi":"10.1186/s12950-025-00442-0","DOIUrl":"https://doi.org/10.1186/s12950-025-00442-0","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is a key driver of disease-related malnutrition and patients with high inflammation may not show the same benefits from nutritional therapy as other patients. We compared in an exploratory manner the prognostic ability of interleukin- 6 (IL- 6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) to predict outcome and response to nutritional therapy, respectively, within a large cohort of patients from a previous nutritional trial.</p><p><strong>Methods: </strong>This is a secondary analysis of the Swiss-wide, multicenter, randomized controlled Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial comparing individualized nutritional support with usual care nutrition in medical inpatients. The primary endpoint was 30-day all-cause mortality.</p><p><strong>Results: </strong>We included 996 patients with an overall mortality rate of 6% within 30 days. Compared to patients with low IL- 6 level < 11.2pg/mL, patients with high levels had a more than 3-fold increase in mortality at 30-days (adjusted HR 3.5, 95% CI 1.95-6.28, p < 0.001), but tended to have a less pronounced mortality benefit from individualized nutritional therapy as compared to usual nutritional care (hazard ratio 0.82 vs. 0.32). CRP and TNF-α were not associated with mortality, but patients with increased CRP levels > 100 mg/dl also showed a trend towards a diminished response to nutritional intervention (hazard ratio 1.25 vs. 0.47).</p><p><strong>Conclusion: </strong>Our findings support the thesis that a high inflammatory state is linked to reduced benefits from nutritional therapy. Apparently, CRP and IL- 6 effectively predict treatment response, but IL- 6 may additionally serve as a prognostic marker for increased mortality. This finding might help to develop improved treatment strategies for patients with elevated inflammatory profiles.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov as NCT02517476 (registered 7 August 2015).</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"16"},"PeriodicalIF":4.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019905","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":"Mucosal immunotherapy targeting APC in lung disease.","authors":"Yangqi Liu, Zijian Chen, Hanchang Cheng, Runzhi Zheng, Weizhe Huang","doi":"10.1186/s12950-025-00432-2","DOIUrl":"https://doi.org/10.1186/s12950-025-00432-2","url":null,"abstract":"<p><p>Several studies have demonstrated that the pulmonary immune response is primarily facilitated by antigen-presenting cells (APCs), and that both professional and non-professional APCs contribute to overall pulmonary immunity. APCs play unique roles and mechanisms in pathogen elimination and immunomodulation. Mucosal immunity exhibits potential advantages over traditional parenteral immunity in that it stimulates immune defenses in mucosal and systemic tissues, which is important for reducing the burden of lung disease. However, obtaining a comprehensive understanding of the crosstalk between mucosal immunity and APC in the context of various lung diseases remains challenging. This mini-review aimed to elucidate the mechanisms of novel mucosal immunity, targeting APC action during lung infections, allergies, and malignant tumorigenesis. This minreview provides important insights into more effective therapeutic approaches for various lung diseases.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"15"},"PeriodicalIF":4.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019907","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":"Exploring the mitigating potential of anthocyanin Malvidin in a mouse model of bleomycin-induced pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and oxidative stress.","authors":"Dingzi Zhou, Lin Cai, Jie Xu, Daigang Fu, Ling Yan, Linshen Xie","doi":"10.1186/s12950-025-00441-1","DOIUrl":"10.1186/s12950-025-00441-1","url":null,"abstract":"<p><strong>Background: </strong>Malvidin (MV), an essential anthocyanin, has antioxidant and anti-inflammatory effects that may help treat pulmonary fibrosis (PF), a progressive and occasionally fatal condition characterized by severe lung scarring, oxidative stress, and inflammation.</p><p><strong>Objective: </strong>This study aims to evaluate the therapeutic potential of MV in PF by assessing its effects on inflammation, oxidative stress, and fibrotic markers through in vitro and in vivo models.</p><p><strong>Methods and materials: </strong>The compound was evaluated by molecular docking. BEAS-2B and RLE-6TN cells were treated with 200 µg/mL BLM to induce inflammation, followed by MV treatment. Cell viability, ROS levels, and wound healing were analyzed. In vivo, BLM-induced mice were evaluated to assess fibrotic and antioxidant biomarkers.</p><p><strong>Results: </strong>MV interacted with NLRP3 with a binding energy of -7 kcal/mol. MV increased cell viability in BLM-induced cells, reducing ROS and oxidative stress. Wound healing was enhanced in MV-treated groups. A decrease in HYP proteins confirms MV's antifibrotic effects. In the mice model, MV reduced TXNIP, MDA, and MPO while increasing CAT, GSH, and SOD, confirming its antioxidant capacity.</p><p><strong>Conclusion: </strong>MV alleviated PF in the BLM-induced model via the NLRP3 inflammasome pathway, demonstrating its potential as an antifibrotic and antioxidant agent.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"14"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756181","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":"Semaphorin 7a is protective through immune modulation during acetaminophen-induced liver injury.","authors":"Eilidh J Livingstone, Jennifer A Cartwright, Lara Campana, Philip J Starkey Lewis, Benjamin J Dwyer, Rhona Aird, Tak Yung Man, Matthieu Vermeren, Adriano Giorgio Rossi, Luke Boulter, Stuart John Forbes","doi":"10.1186/s12950-025-00429-x","DOIUrl":"10.1186/s12950-025-00429-x","url":null,"abstract":"<p><strong>Background and aim: </strong>Acetaminophen (APAP) induced acute liver injury (ALI), the leading cause acute liver failure in the western world, has limited treatment options. APAP toxicity results in massive hepatic necrosis and secondary infiltrating monocytes and neutrophils, which contribute to pathogenesis. Semaphorin 7a (Sema7a), a chemoattractant and modulator of monocytes and neutrophils, is a potential therapeutic target in other conditions, but its role in APAP-ALI is unexplored.</p><p><strong>Methods: </strong>Wild-type (WT) and Sema7a knockout (KO) mice were examined during APAP-ALI. Serum liver function tests, histological analysis and cellular localisation of Sema7a and its receptors, Plexin C1 and Integrin β1, were examined. Serum cytokines were quantified, tissue macrophages and neutrophils were localised, and in vivo phenotype, including phagocytosis, was assessed by immunohistochemistry and flow cytometry.</p><p><strong>Results: </strong>Sema7a was expressed by HNF4α + peri-necrotic hepatocytes circumferentially during APAP-ALI injury phases, and serum concentrations were increased, and correlated with hepatic injury. Sema7a KO mice had increased circulating inflammatory cytokines and significantly less hepatic F4/80 + macrophages, a cell type required for hepatic repair. Sema7a KO mice had higher necrotic area neutrophils, and increased neutrophil chemoattractant CXCL1. Without Sema7a expression, mice displayed increased necrosis and liver injury markers compared to Sema7a WT mice. Without peri-necrotic hepatocyte Sema7a expression, we also identified increased cell death and hepatic cellular stress outside of necrosis.</p><p><strong>Conclusion: </strong>We have identified a novel protective role of Sema7a during injury phases of APAP-ALI. Without peri-necrotic hepatocyte Sema7a expression and secretion, there is increased inflammation, time specific worsened hepatic necrosis and increased hepatic cell stress and death outside of the necrotic zone.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"13"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671731","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":"Prehospital pulse-dose glucocorticoid on index of microvascular resistance in patients with ST-segment elevation myocardial infarction: a sub-study of the PULSE-MI trial.","authors":"Jasmine Melissa Marquard, Jacob Lønborg, Laust Emil Roelsgaard Obling, Rasmus Paulin Beske, Yan Zhou, Lars Nepper-Christensen, Niels Vejlstrup, Lia Evi Bang, Christian Hassager, Fredrik Folke, Lars Bredevang Andersen, Helle Collatz Christensen, Lene Holmvang, Frants Pedersen, Ole Ahlehoff, Reza Jabbari, Mikko Minkkinen, Rikke Sørensen, Hans-Henrik Tilsted, Thomas Engstrøm","doi":"10.1186/s12950-025-00440-2","DOIUrl":"10.1186/s12950-025-00440-2","url":null,"abstract":"<p><strong>Background: </strong>Microvascular injury in patients with ST-segment elevation myocardial infarction (STEMI) occurs in up to 50%, yet no therapeutic target exists. Inflammation contributes directly to myocardial damage in STEMI and may also cause deleteriously effects on the microcirculation. The aim of this prespecified sub-study was to determine the effect of prehospital pulse-dose glucocorticoid on the microcirculation determined by index of microvascular resistance (IMR) and its relation to inflammation. The PULSE-MI trial was a 1:1 randomized, blinded, placebo-controlled clinical trial in patients with STEMI transferred for primary percutaneous coronary intervention (PCI) investigating the cardioprotective effects of prehospital pulse-dose glucocorticoid (methylprednisolone 250 mg) compared with placebo. In this prespecified sub-study, we investigated microvascular function as IMR by thermodilution after primary PCI and inflammation defined by C-reactive protein (CRP) at 24 hours after onset of STEMI.</p><p><strong>Results: </strong>Of 530 patients included in the PULSE-MI trial, 295 (56%) were assessed with coronary physiology of whom 142 (48%) were treated with glucocorticoid and 153 (52%) with placebo. Baseline characteristics were overall well-balanced in both groups. The median IMR in the glucocorticoid group was 23 (interquartile range (IQR), 11-38) and 18 (IQR, 11-42) in the placebo group (p=0.49). CRP upon arrival did not differ between treatment groups (p=0.81), but CRP at 24 hours was significantly lower in the glucocorticoid group compared to placebo (p<0.001).</p><p><strong>Conclusions: </strong>Prehospital glucocorticoid did not impact IMR assessed immediately after primary PCI, albeit this compound, demonstrated significant anti-inflammatory effects as determined by CRP levels at 24 hours.</p><p><strong>Trial registration: </strong>http://www.</p><p><strong>Clinicaltrials: </strong>gov ; Unique Identifier: NCT05462730.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"12"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659792","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":"Contribution of brain pericytes to neuroinflammation following repetitive head trauma.","authors":"Arianna Cembran, Maxwell Eisenbaum, Daniel Paris, Michael Mullan, Fiona Crawford, Scott Ferguson, Corbin Bachmeier","doi":"10.1186/s12950-025-00439-9","DOIUrl":"10.1186/s12950-025-00439-9","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is a prominent pathological hallmark of traumatic brain injury (TBI) and glia cells have been widely characterized in the onset or progression of brain inflammation. While an effect of inflammation on cerebrovascular breakdown has been observed, little is known about the specific contribution of brain pericytes to the inflammatory response in TBI. Here, we focused on studying the pericyte response to inflammatory stimuli commonly found in the brain following TBI.</p><p><strong>Methods: </strong>Mouse brain vascular pericytes were exposed to IL-1β, TNF-α and IFN-γ for 2 h and 24 h and probed for markers of pericyte health and a panel of inflammatory mediators. As the platelet-derived growth factor (PDGF) pathway is critical to pericyte function, we also assessed the effect of PDGF-BB stimulation on the inflammatory response in pericytes. Cultured pericytes were treated with PDGF-BB (10 ng/mL) prior to, simultaneously, and following inflammatory insult. To further investigate their role in brain immunosurveillance, we analyzed the cytokine secretome in mouse pericyte cultures treated with PDGF-BB, as well as in brain vascular pericytes isolated from repetitive mild TBI (r-mTBI) mice that were fed phenytoin-enriched chow, an inducer of PDGF-BB secretion.</p><p><strong>Results: </strong>Cytokine stimulation with TNF-α, IL-1β, and IFN-γ for 2 and 24 h led to significant upregulation of PDGFRβ in cultured pericytes, with an 8-fold increase after 24 h. MTT assays showed no significant change in cell viability, indicating that cytokine treatment did not induce cytotoxicity. Further, elevated levels of pro-inflammatory markers STAT1 and p-NFkB were observed in response to cytokine exposure, with a concurrent increase in VCAM1 and MMP9 expression. PDGF-BB treatment significantly attenuated the inflammatory response in pericytes, reducing PDGFRβ levels and the activation of inflammatory pathways, including STAT1 and NFkB. Cytokine secretion profiles also revealed that PDGF-BB, when administered post-inflammatory insult, selectively reduced pro-inflammatory cytokines such as IL-1β and IFN-γ. Additionally, phenytoin treatment in r-mTBI mice decreased IL-1β, TNF-α, IL-5, and KC/GRO levels in isolated brain pericytes, while IL-2, IL-4, and IL-6 levels were unchanged compared to untreated r-mTBI animals.</p><p><strong>Conclusions: </strong>Our results indicate an immunoreactive role for brain pericytes in the propagation of neuroinflammation. Moreover, following brain insults, we found PDGF-BB stimulation can normalize pericyte function and reduce cerebrovascular inflammation, a key factor in secondary brain injury. Targeting brain pericytes may provide novel therapeutic opportunities to improve cerebrovascular health and reduce brain inflammation in the aftermath of TBI.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"11"},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544608","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}