Inflammation Research最新文献

{"title":"IL-35 modulates Tfh2 and Tfr cell balance to alleviate allergic rhinitis.","authors":"Xiangqian Qiu, Jinyuan Li, Yinhui Zeng, Qingxiang Zeng, Xi Luo, Wenlong Liu","doi":"10.1007/s00011-025-01997-7","DOIUrl":"https://doi.org/10.1007/s00011-025-01997-7","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) represents a persistent inflammatory condition affecting the upper respiratory tract, characterized by abnormal initiation of the immunoglobulin E (IgE)-mediated cascade. Follicular helper T (Tfh) cells and regulatory T (Tfr) cells are pivotal in orchestrating the development of IgE production in AR patients. IL-35, an anti-inflammatory cytokine, secreted by various cellular subpopulations.</p><p><strong>Objective: </strong>To investigate the interplay and underlying mechanisms between interleukin-35 (IL-35) and Tfr/Tfh2 cells in the context of AR.</p><p><strong>Methods: </strong>Experimental animal models employing BALB/c mice and IL-35-deficient mice underwent sensitization and challenge procedures utilizing ovalbumin (OVA) as the antigen in vivo. IL-35 was administered intranasally prior to OVA challenges. Nasal histopathological examination, PBMC isolation, Tfr/Tfh2 cell staining, Tfr/Tfh2 sorting and culture, and qPCR analysis as well as enzyme-linked immunosorbent assay (ELISA) were conducted for exploring the effect of IL-35 on Tfr/Tfh2 cells.</p><p><strong>Results: </strong>Administration of IL-35 suppressed OVA-elicited allergic inflammation in murine models. IL-35 treatment led to an elevation in the proportion of peripheral blood Tfr cells and a decrease in Tfh2 cells. IL-35 also downregulated IL-4 and IL-21 protein expression by Tfh2 cells and upregulated IL-10 and transforming growth factor-β (TGF-β) production by Tfr cells. The anti-ICOS treatment abrogated the effect of IL-35 on Tfh2 and Tfr cells.</p><p><strong>Conclusion: </strong>Our study provided novel insights into the mechanisms of IL-35 action and its promoting effects on Tfh2 and inhibiting effects on Tfr cells by targeting key transcription factors, contributing to the understanding of the pathogenesis and treatment of AR.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"21"},"PeriodicalIF":4.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004793","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":"IL-8 promotes pyroptosis through ERK pathway and mediates glucocorticoid resistance in chronic rhinosinusitis with nasal polyps.","authors":"Wei Zhang, Yun Lei, Ting Zhang, Bo You, Jie Zhang, Yong Zhou, Shaocong Zhang, Xueru Li, Yuting Liu, Lianqin Shen, Jianmei Zhao, Jing Chen","doi":"10.1007/s00011-024-01982-6","DOIUrl":"https://doi.org/10.1007/s00011-024-01982-6","url":null,"abstract":"<p><strong>Objective: </strong>This study seeks to elucidate the role and molecular mechanisms of IL-8 in nasal epithelial cell pyroptosis and its impact on glucocorticoid (GC) resistance.</p><p><strong>Methods: </strong>We assessed the expression of pyroptosis-related biomarkers and IL-8 in tissues and human nasal epithelial cells (hNECs) from both control and nasal polyp patients using western blot. Their localization was determined through immunohistochemistry and immunofluorescence. Cell death and cytotoxicity assay, electron microscopy, ELISA, and immunofluorescence were utilized to investigate IL-8-induced pyroptosis and GC resistance in hNECs, alongside the examination of the involved signaling pathways via western blot and immunofluorescence. In a murine model, hematoxylin-eosin staining and immunohistochemistry clarified relationship between pyroptosis and GC resistance.</p><p><strong>Results: </strong>IL-8 and pyroptotic biomarker expression were significantly higher in nasal polyp-derived tissues and hNECs compared to controls. IL-8 showed a positive correlation and co-localized with the pyroptotic biomarkers. IL-8 triggered pyroptosis in hNECs by activating the ERK signaling pathway, leading to increased IL-1β and IL-18 secretion. Moreover, IL-8-induced pyroptosis was found to contribute to GC resistance by affecting phosphorylation of GC receptor Ser211. Inhibition of pyroptotic proteins mitigated IL-8-induced GC resistance both in vitro and in vivo.</p><p><strong>Conclusion: </strong>Elevated IL-8 facilitates pyroptosis via the ERK signaling pathway and plays a significant role in GC resistance in nasal polyps.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"20"},"PeriodicalIF":4.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004796","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 role of mTOR activation in steroid-resistant asthma: insights from particulate matter-induced mouse model and patient studies.","authors":"Heung-Woo Park, Suh-Young Lee, Hyun Seung Lee","doi":"10.1007/s00011-025-01992-y","DOIUrl":"https://doi.org/10.1007/s00011-025-01992-y","url":null,"abstract":"<p><p>Particulate matter (PM) exposure has been proposed as one of the causes of steroid resistance. However, studies investigating this using patient samples or animals are still lacking. Therefore, in this study, we aimed to investigate the changes in cytokines and mTOR (mammalian target of rapamycin) activation in patients with steroid resistant asthma and the role of mTOR in a mouse model of steroid resistant asthma induced by PM. In mouse experiment, on administering PM10 and allergen (Dp) through the intranasal route for 3 weeks, airway hyperresponsiveness (AHR), eosinophils, and airway inflammation were increased. However, administering rapamycin (mTOR inhibitor) together with PM and Dp led to significant decrease in all of the abovementioned features; additionally, the population of IL-13 + or IL-17 + cells in CD62^lowCD44^high subset of CD4 + T cells, which serves as an effector/memory cell marker, showed a significant decrease when compared to the group that received PM and Dp. When Dp was administered once after a rest period, the mice exposed to PM and Dp exhibited resurgence in asthma features and elevated effector/memory IL-13 + or IL-17 + cell populations. Rapamycin administration inhibited this effect. In human PBMC, in the steroid Non-Responder (NR) group, cytokines with p-mTOR double-positive population of effector/memory CD4 T cells (CCR7-CD45RA-CD4 + in CD62-CD27-CD45RO+) was significantly higher than that of the Normal or steroid Responder (R) groups. These data demonstrates that rapamycin can inhibit asthmatic features in mouse model of PM induced steroid-resistant asthma. And we suggest that rapamycin could act on effector/memory CD4 + T cells through in vitro and patient sample experiments.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"19"},"PeriodicalIF":4.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983355","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":"Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases.","authors":"Xiuju Guan, Haitao Li, Lijuan Zhang, Hongwei Zhi","doi":"10.1007/s00011-025-01993-x","DOIUrl":"https://doi.org/10.1007/s00011-025-01993-x","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) continue to be a substantial global healthcare burden despite considerable progress in therapies. The inflammatory response during the progression of CVD has attracted considerable attention. Mitochondria serve as the principal energy source for the heart. In cardiovascular illnesses, mitochondrial homeostasis is disrupted, accompanied by structural and functional impairments. During mitochondrial stress or injury, mitochondrial damage-associated molecular patterns (mtDAMPs), such as mitochondrial DNA, cardiolipin, N-formyl peptide, and adenosine triphosphate, are released to activate pattern recognition receptors and trigger immunological responses. Inflammatory responses mediated by mtDAMPs substantially contribute to the pathophysiology of cardiovascular illnesses. In this review, we discuss the molecular mechanisms by which different mtDAMPs control the inflammatory response, address the pathological consequences of mtDAMPs in inducing or exacerbating the inflammatory response in CVDs, and summarize potential therapeutic targets in relevant experimental studies. Preventing or reducing mtDAMP release may play a role in CVD progression by alleviating the inflammatory response.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"18"},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978330","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":"Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.","authors":"Toshiaki Iba, Julie Helms, Cheryl L Maier, Ricard Ferrer, Jerrold H Levy","doi":"10.1007/s00011-025-01994-w","DOIUrl":"https://doi.org/10.1007/s00011-025-01994-w","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria generate the adenosine triphosphate (ATP) necessary for eukaryotic cells, serving as their primary energy suppliers, and contribute to host defense by producing reactive oxygen species. In many critical illnesses, including sepsis, major trauma, and heatstroke, the vicious cycle between activated coagulation and inflammation results in tissue hypoxia-induced mitochondrial dysfunction, and impaired mitochondrial function contributes to thromboinflammation and cell death.</p><p><strong>Methods: </strong>A computer-based online search was performed using the PubMed and Web of Science databases for published articles concerning sepsis, trauma, critical illnesses, cell death, mitochondria, inflammation, coagulopathy, and organ dysfunction.</p><p><strong>Results: </strong>Mitochondrial outer membrane permeabilization triggers apoptosis by releasing cytochrome c and activating caspases. Apoptosis is a non-inflammatory programmed cell death but requires sufficient ATP supply. Therefore, conversion to inflammatory necrosis may occur due to a lack of ATP in critical illness. Severely damaged mitochondria release excess reactive oxygen species and injurious mitochondrial DNA, inducing cell death. Besides non-programmed necrosis, mitochondrial damage can trigger programmed inflammatory cell death, including necroptosis, pyroptosis, and ferroptosis. Additionally, a unique form of DNA-ejecting cell death, known as etosis, occurs in monocytes and granulocytes following external stimuli and mitochondrial damage. The type of cell death chosen remains uncertain but is known to depend on the cell type, the nature of the injury, and the degree of damage.</p><p><strong>Conclusions: </strong>Mitochondria damage is the major contributor to the cell death mechanism that leads to organ damage in critical illnesses. Regulating and restoring mitochondrial function holds promise for developing new therapeutic approaches for mitigating critical diseases.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"17"},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978331","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":"IL-17 as a putative hallmark of intense arthralgia and age-related serum immune mediator networks during acute chikungunya fever.","authors":"Caio Wilker Teixeira, Jonai Pacheco Dias, Lizandra Morgado-Santos, Ismael Artur da Costa-Rocha, Sarah Giarola-Silva, Ágata Lopes-Ribeiro, Letícia Gomes-de-Pontes, Thaiza Aline Pereira Santos, Joaquim Pedro Brito-de-Sousa, Erik Vinicius de Sousa Reis, Ana Carolina Campi-Azevedo, Andréa Teixeira-Carvalho, Vanessa Peruhype-Magalhães, Adriana de Souza Azevedo, Waleska Dias Schwarcz, Sheila Maria Barbosa de Lima, Flávio Guimarães da Fonseca, Ana Maria Caetano de Faria, Carolina Lucas, João Felipe Bezerra, Olindo Assis Martins-Filho, Josélio Maria Galvão de Araújo, Jordana Grazziela Alves Coelho-Dos-Reis","doi":"10.1007/s00011-024-01977-3","DOIUrl":"https://doi.org/10.1007/s00011-024-01977-3","url":null,"abstract":"<p><strong>Introduction: </strong>The present study aimed at evaluating the systemic profile and network connectivity of immune mediators during acute chikungunya fever (CHIKF) according to days of symptoms onset and ageing.</p><p><strong>Methods: </strong>A total of 161 volunteers (76 CHIKF patients and 85 non-infected healthy controls) were enrolled.</p><p><strong>Results and discussion: </strong>Data demonstrated that a massive and polyfunctional storm of serum immune mediators was observed in CHIKF. Distinct patterns of mediators were observed according to days of symptoms onset. Most chemokines and proinflammatory cytokines were increased early at D0-1, with some increased throughout the kinetics timeline, while others presented a waning profile towards D4-12. Rhythmic signatures further underscored these findings. Increased levels IL-17 appeared as a hallmark of intense arthralgia, while CCL5&IL-5 and TNF-α&IL-10 duets are age-tunning features in CHIKF. Differential connectivity of networks was observed with ageing, with a progressive increase in the overall connectivity from < 8 yo towards 51-89 yo. Of note, subsets of immune mediators (IL-17, IL-2 and IL-5) displayed hotspots of hyperconnectivity in elderly as compared to younger patients.</p><p><strong>Conclusion: </strong>Together, the overall scenario reveals unique patterns of soluble immune mediators during acute CHIKF infection with an oscillating symphony according to days of symptoms and ageing, which brings insight to future tailor-made therapeutic interventions.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"16"},"PeriodicalIF":4.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964628","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":"IL-33, a neutrophil extracellular trap-related gene involved in the progression of diabetic kidney disease.","authors":"Yufei Ye, Anwen Huang, Xinyan Huang, Qin Jin, Hongcheng Gu, LuLu Liu, Bing Yu, Longyi Zheng, Wei Chen, Zhiyong Guo","doi":"10.1007/s00011-024-01981-7","DOIUrl":"https://doi.org/10.1007/s00011-024-01981-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronic inflammation is well recognized as a key factor related to renal function deterioration in patients with diabetic kidney disease (DKD). Neutrophil extracellular traps (NETs) play an important role in amplifying inflammation. With respect to NET-related genes, the aim of this study was to explore the mechanism of DKD progression and therefore identify potential intervention targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Hub NET-related DEGs were screened via differential expression analysis and three machine learning methods, namely, LASSO, SVM-RFE and random forest. Consensus clustering was performed to analyze NET-related subtypes in DKD patients. KEGG enrichment analysis, GSEA, GSVA, ssGSEA and ESTIMATE were conducted to explore the molecular features of DKD patient subtypes. Leveraging single-nucleus RNA-seq datasets, the \"scissor\" and \"bisqueRNA\" algorithms were applied to identify the composition of renal cell types in DKD patient subtypes. Soft clustering analysis was performed to obtain gene groups with similar expression patterns during the development and progression of DKD. The correlations between hub NET-related DEGs and clinical parameters were mined from the Nephroseq V5 database. The core gene among the hub NET-related DEGs was selected by calculating semantic similarity. \"Cellchat\" algorithm, immunostaining, ELISA and flow cytometry were performed to explore the expression and function of the core gene. The Drug-Gene Interaction Database (DGIdb) was searched to identify candidate drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Six hub NET-related DEGs, namely, ACTN1, ITGB2, IL33, HRG, NFIL3 and CLEC4E, were identified. On the basis of these 6 genes, DKD patients were classified into 2 clusters. Cluster 1 patients, with higher NET scores, were evidently more immune-activating than those of cluster 2. Markedly increased numbers of immune cells, fibroblasts and proinflammatory proximal tubular cells were observed in cluster 1 but not in cluster 2. Cluster 1 also represented a more clinically advanced disease state. Among the 6 hub NET-related DEGs, the mRNA expression of ACTN1, ITGB2, IL33 and HRG was correlated with the eGFR. By semantic similarity analysis, IL33 was considered a central gene among the 6 genes. Cell-cell communication analysis further indicated that intercellular interactions via IL-33 were enhanced in DKD. Serum IL-33 concentration was negatively correlated with eGFR. IHC staining revealed that IL-33 expression was upregulated in the tubular epithelium in DKD patients. Supernatants from inflammatory tubular epithelial cells can increase MPO in neutrophils, whereas addition of anti-IL-33 antibody attenuated this phenotype.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We identified 2 distinct NET-related subtypes in DKD patients, in which one subgroup was apparently more inflammatory and associated with a more severe clinical state. A significantly increased level of IL-33 in this inflammatory patient","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"15"},"PeriodicalIF":4.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964629","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":"Rare constituents of the nasal microbiome contribute to the acute exacerbation of chronic rhinosinusitis.","authors":"Yunfan Zhang, Fan Yuan, Zheng Liu, Xiaoxi Huang, Junsheng Hong, Feifan Chang, Dawei Wu","doi":"10.1007/s00011-025-01995-9","DOIUrl":"https://doi.org/10.1007/s00011-025-01995-9","url":null,"abstract":"<p><strong>Background: </strong>Dysbiosis of the nasal microbiome is considered to be related to the acute exacerbation of chronic rhinosinusitis (AECRS). The microbiota in the nasal cavity of AECRS patients and its association with disease severity has rarely been studied. This study aimed to characterize nasal dysbiosis in a prospective cohort of patients with AECRS.</p><p><strong>Methods: </strong>We performed a cross-sectional study of 28 patients with AECRS, 20 patients with chronic rhinosinusitis (CRS) without acute exacerbation (AE), and 29 healthy controls using 16S rRNA gene sequencing. Subjective and objective assessments of CRS disease severity during AE were also collected.</p><p><strong>Results: </strong>Compared to healthy controls and patients with CRS without AE, AECRS presented with a substantial decrease of the Corynebacterium_1 and a significant increase of Ralstonia and Acinetobacter at the genus level (LDA score > 2.0 [P < 0.05]). Furthermore, genera with a mean relative abundance (MRA) of less than 1% were defined as rare components based on published studies, then 29 genera with a substantial alteration in AECRS were rare constituents of the microbiome, of which 18 rare genera were highly associated with subjective and objective disease severity. Moreover, a combination of 15 genera could differentiate patients with AECRS with an area under the curve of 0.870 (95% CI = 0.784-0.955). Prediction of microbial functional pathways involved significantly enhanced lipopolysaccharide biosynthesis pathways and significantly decreased folate biosynthesis, sulfur relay system, and cysteine and methionine metabolism pathways in patients with AECRS.</p><p><strong>Conclusions: </strong>The rare nasal microbiota (MRA < 1%) correlated with disease status and disease severity in patients with AECRS. The knowledge about the pattern of the nasal microbiome and its metabolomic pathway may contribute to the fundamental understanding of AECRS pathophysiology.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"14"},"PeriodicalIF":4.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964604","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":"Comparative analysis of adenosine 1 receptor expression and function in hippocampal and hypothalamic neurons.","authors":"Lea Wegmann, Helmut L Haas, Olga A Sergeeva","doi":"10.1007/s00011-024-01980-8","DOIUrl":"10.1007/s00011-024-01980-8","url":null,"abstract":"<p><strong>Background: </strong>Adenosine, an ATP degradation product, is a sleep pressure factor. The adenosine 1 receptor (A1R) reports sleep need. Histaminergic neurons (HN) of the tuberomamillary nucleus (TMN) fire exclusively during wakefulness and promote arousal. All of them express GABA_A receptors and are inhibited by GABA. Does adenosine contribute to their silencing?</p><p><strong>Subjects and treatment: </strong>Responses to adenosine were studied in mouse brain slices and primary dissociated cultures. For HN identification single-cell (sc)RT-PCR, reporter protein and pharmacology were used. Hippocampal Dentate Gyrus granular layer cells (DGgc) were studied in parallel.</p><p><strong>Methods: </strong>Firing frequency was recorded in patch-clamp configuration or by microelectrode arrays. A1R-expression was studied by scRT-PCR and semiquantitative PCR.</p><p><strong>Results: </strong>Most DGgc were inhibited through A1R, detected with scRT-PCR in 7 out of 10 PDZd2-positive DGgc; all HN were A1R negative. One HN out of 25 was inhibited by adenosine. The A1R mRNA level in the hippocampus was 6 times higher than in the caudal (posterior) hypothalamus. Response to adenosine was weaker in hypothalamic compared to hippocampal cultures.</p><p><strong>Conclusions: </strong>Most HN are not inhibited by adenosine.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"11"},"PeriodicalIF":4.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947870","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":"Lysine acetylation and its role in the pathophysiology of acute pancreatitis.","authors":"Xiaoqian Li, Xiaolu Li, Zhang Jinfeng, Tao Yu, Bei Zhang, Yanyan Yang","doi":"10.1007/s00011-024-01989-z","DOIUrl":"10.1007/s00011-024-01989-z","url":null,"abstract":"<p><p>Acute pancreatitis (AP) represents a severe inflammatory condition of the exocrine pancreas, precipitating systemic organ dysfunction and potential failure. The global prevalence of acute pancreatitis is on an ascending trajectory. The condition carries a significant mortality rate during acute episodes. This underscores the imperative to elucidate the etiopathogenic pathways of acute pancreatitis, enhance comprehension of the disease's intricacies, and identify precise molecular targets coupled with efficacious therapeutic interventions. The pathobiology of acute pancreatitis encompasses not only the ectopic activation of trypsinogen but also extends to disturbances in calcium homeostasis, mitochondrial impairment, autophagic disruption, and endoplasmic reticulum stress responses. Notably, the realm of epigenetic regulation has garnered extensive attention and rigorous investigation in acute pancreatitis research over recent years. One of these modifications, lysine acetylation, is a reversible post-translational modification of proteins that affects enzyme activity, DNA binding, and protein stability by changing the charge on lysine residues and altering protein structure. Numerous studies have revealed the importance of acetylation modification in acute pancreatitis, and that it is a favorable target for the design of new drugs for this disease. This review centers on lysine acetylation, examining the strides made in acute pancreatitis research with a focus on the contributory role of acetylomic alterations in the pathophysiological landscape of acute pancreatitis, thereby aiming to delineate novel therapeutic targets and advance the development of more efficacious treatment modalities.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"13"},"PeriodicalIF":4.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947955","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}