Inflammation Research最新文献

{"title":"Lipopolysaccharide (LPS) induces sclerostin secretion by extracellular vesicle via TLR4/miR-92a-3p/PTEN/NF-κB signalling pathway in murine macrophage.","authors":"Carsten Tsun-Ka Kwok, Chun-Chak Wong, Jing-Jing Li, Yiu-Wa Kwan, George Pak-Heng Leung, Bun Tsoi, Franklin Wang-Ngai Chow, Sai-Wang Seto","doi":"10.1007/s00011-024-01987-1","DOIUrl":"https://doi.org/10.1007/s00011-024-01987-1","url":null,"abstract":"<p><strong>Background: </strong>Sclerostin (SOST) is traditionally regarded as an osteocyte-derived secreted glycoprotein that regulates bone mineralization. Recent studies reported that SOST is also released from non-skeletal sources, especially during inflammation. However, the cellular source and regulatory mechanisms governing SOST generation in inflammation remain unclear. This study investigated whether macrophages produce SOST in response to inflammatory stimuli and determined associated regulatory pathways.</p><p><strong>Methods: </strong>The effect of lipopolysaccharide (LPS)-induced inflammation in SOST generation and its underlying regulatory mechanism was examined on mouse macrophage RAW 264.7 by western blot and immunofluorescent staining. Transfection with miR-92a-3p mimic and inhibitor were used to validate its role in SOST production. The role of NF-κB and TLR4 were studied using pharmacological inhibitors BAY 11-7085 and TAK242, respectively. The involvement of NF-κB and TLR4 in LPS-induced SOST production was further validated through nuclear NF-κB p65 immunoprecipitation and TLR4 small interfering RNA (siRNA) experiments, respectively.GW4869 and manumycin A (extracellular vesicles (EV) biogenesis inhibitors) were used to examine the associated of SOST and EV. Finally, SOST expression and characteristics of the isolated EV were assessed by Western blot and nanoparticle tracking analysis (NTA).</p><p><strong>Results: </strong>LPS significantly induced SOST protein expression and secretion in RAW 264.7. MiR-92a-3p was upregulated by LPS stimulation in macrophages. Transfection of miR-92a-3p mimic increased SOST generation in RAW 264.7. Inhibition of TLR4 and NF-κB signalling pathways using pharmacological inhibitors significantly suppressed LPS-induced SOST in RAW 264.7. Similarly, TLR4 siRNA effectively suppressed LPS-induced SOST level. However, the LPS-induced upregulation of miR-92a-3p was only regulated by TLR4, but not by NF-κB. NF-κB was found to directly bind to the mouse sost promoter, thereby activating sost transcription. Additionally, SOST secretion was found predominantly associated with EV from LPS-stimulated cells, and inhibition of EV biogenesis suppressed SOST production in RAW 264.7 cells.</p><p><strong>Conclusions: </strong>In conclusion, our study showed, for the first time, that LPS induced SOST generation and secretion via TLR4/miR-92a-3p/PTEN/NF-κB singling pathway in murine macrophage RAW 264.7 cells. Moreover, we showed that SOST is secreted from the RAW 264.7 cells in the form of extracellular vesicle. This study identified macrophage as a novel source of SOST, highlighting its potential role in inflammatory diseases.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"27"},"PeriodicalIF":4.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038274","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 celastrol in inflammation and diseases.","authors":"Han Lei, Yantian Ruan, Ruidong Ding, Haotian Li, Xiaoguang Zhang, Xinying Ji, Qi Wang, Shuangyu Lv","doi":"10.1007/s00011-024-01983-5","DOIUrl":"https://doi.org/10.1007/s00011-024-01983-5","url":null,"abstract":"<p><p>Celastrol is one of the main active ingredients extracted from the plant Tripterygium wilfordii Hook F. A growing number of studies have shown that celastrol has various pharmacological effects, including anti-inflammation, anti-rheumatism, treatment of neurodegenerative diseases, and anti-tumor. This article systematically summarized the mechanism and role of celastrol in lipid metabolism and obesity, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, inflammatory bowel disease, neurodegenerative diseases, and cancer and other diseases (such as diabetes, respiratory-related diseases, atherosclerosis, psoriasis, hearing loss, etc.). The celastrol played roles in inflammation response, cell apoptosis, autophagy, ferroptosis, and lipid metabolism mainly by acting on chondrocytes, macrophages, mitochondria, and endoplasmic reticulum (ER) through NF-κB, STAT, MAPK, TLR, PI3K-AKT-mTOR, and other signal pathways. This review could provide a reference for the clinical application and further development and utilization of celastrol.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"23"},"PeriodicalIF":4.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038277","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":"Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.","authors":"Vinícius Amorim Beltrami, Flávia Rayssa Braga Martins, Débora Gonzaga Martins, Celso Martins Queiroz-Junior, Franciel Batista Félix, Letícia Cassiano Resende, Felipe Rocha da Silva Santos, Larisse de Souza Barbosa Lacerda, Victor Rodrigues de Melo Costa, Walison Nunes da Silva, Pedro Pires Goulart Guimaraes, Goulart Guimaraes, Frederico Marianetti Soriani, Mauro Martins Teixeira, Vivian Vasconcelos Costa, Vanessa Pinho","doi":"10.1007/s00011-024-01985-3","DOIUrl":"https://doi.org/10.1007/s00011-024-01985-3","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to understand the potential therapeutic and anti-inflammatory effects of the phosphodiesterase-4 (PDE4) inhibitor roflumilast in models of pulmonary infection caused by betacoronaviruses.</p><p><strong>Methods: </strong>Mice were infected intranasally with murine hepatitis virus (MHV-3) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Roflumilast was given to MHV-3-infected mice therapeutically at doses of 1 mg/kg or 10 mg/kg, or prophylactically at 10 mg/kg. In SARS-CoV-2-infected mice, roflumilast was given therapeutically at a dose of 10 mg/kg. Lung histopathology, chemokines (CXCL-1 and CCL2), cytokines (IL-1β, IL-6, TNF, IFN-γ, IL-10 and TGFβ), neutrophil immunohistochemical staining (Ly6G⁺ cells), macrophage immunofluorescence staining (F4/80⁺ cells), viral titration plaque assay, real-time PCR virus detection, and blood cell counts were examined.</p><p><strong>Results: </strong>Therapeutic treatment with roflumilast at 10 mg/kg reduced lung injury in SARS-CoV-2 or MHV-3-infected mice without compromising viral clearance. In MHV-3-infected mice, reduced lung injury was associated with decreased chemokines levels, prevention of neutrophil aggregates and reduced macrophage accumulation in the lung tissue. However, the prophylactic treatment strategy with roflumilast increased lung injury in MHV-3-infected mice.</p><p><strong>Conclusion: </strong>Our findings indicate that therapeutic treatment with roflumilast reduced lung injury in MHV-3 and SARS-CoV-2 lung infections. Given the protection induced by roflumilast in inflammation, PDE4 targeting could be a promising therapeutic avenue worth exploring following severe viral infections of the lung.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"24"},"PeriodicalIF":4.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038276","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 NLRP3 inflammasome-mediated pyroptosis in astrocytes during hyperoxia-induced brain injury.","authors":"Qiao Liu, Yan Tan, Zhan-Wei Zhang, Wang Tang, Lei Han, Ke-Ping Peng, Ming-Hui Liu, Gui-Xiang Tian","doi":"10.1007/s00011-024-01984-4","DOIUrl":"https://doi.org/10.1007/s00011-024-01984-4","url":null,"abstract":"<p><strong>Background: </strong>Hyperoxia-induced brain injury is a severe neurological complication that is often accompanied by adverse long-term prognosis. The pathogenesis of hyperoxia-induced brain injury is highly complex, with neuroinflammation playing a crucial role. The activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, which plays a pivotal role in regulating and amplifying the inflammatory response, is the pathological core of hyperoxia-induced brain injury. Additionally, astrocytes actively participate in neuroinflammatory responses. However, there is currently no comprehensive overview summarizing the role of astrocytes in hyperoxia-induced brain injury and the NLRP3 signaling pathways in astrocytes.</p><p><strong>Objective: </strong>This article aims to provide an overview of studies reported in the literature investigating the pathological role of astrocyte involvement during the inflammatory response in hyperoxia-induced brain injury, the mechanisms of hyperoxia activateing the NLRP3 inflammasome to mediate pyroptosis in astrocytes, and the potential therapeutic effects of drugs targeting the NLRP3 inflammasome to alleviate hyperoxia-induced brain injury.</p><p><strong>Method: </strong>We searched major databases (including PubMed, Web of Science, and Google Scholar, etc.) for literature encompassing astrocytes, NLRP3 inflammasome, and pyroptosis during hyperoxia-induced brain injury up to Oct 2024. We combined with studies found in the reference lists of the included studies.</p><p><strong>Conclusion: </strong>In this study, we elucidated the transition of function in astrocytes and activation mechanisms under hyperoxic conditions, and we summarized the potential upstream of the trigger involved in NLRP3 inflammasome activation during hyperoxia-induced brain injury, such as ROS and potassium efflux. Furthermore, we described the signaling pathways of the NLRP3 inflammasome and pyroptosis executed by GSDMD and GSDME in astrocytes under hyperoxic conditions. Finally, we summarized the inhibitors targeting the NLRP3 inflammasome in astrocytes to provide new insights for treating hyperoxia-induced brain injury.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"25"},"PeriodicalIF":4.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038278","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-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}