Inflammation Research最新文献

{"title":"Modulation of Plet1 expression by N-Acetylglucosamine through the IL-17 A-MAPK pathway in an imiquimod-induced psoriasis mouse model.","authors":"Balachandar Selvakumar, Bilal Rah, Jayalakshmi Jagal, Priyadarshini Sekar, Raneem Moustafa, Rakhee Kizhuvappat Ramakrishnan, Mohamed Haider, Saleh Mohamed Ibrahim, Rani Samsudin","doi":"10.1007/s00011-024-01958-6","DOIUrl":"10.1007/s00011-024-01958-6","url":null,"abstract":"<p><p>Psoriasis (Ps) is a chronic inflammatory disorder marked by skin plaque formation, driven by immune dysregulation and genetic factors. Despite the available treatments, incidence of Ps is increasing in the dermatology patients. Novel strategies are crucial due to current treatment limitations. The interleukin 17 (IL-17) pathway is pivotal in Ps pathogenesis, however the expression of its putative target gene placenta expressed transcript 1 (Plet1) remains unstudied in Ps. Considering the potential anti-inflammatory properties of N-Acetylglucosamine (GlcNAc), our study explored its role in modulating Plet1 expression in an imiquimod (IMQ)-induced Ps mouse model. Our data demonstarted a significant reduction of inflammation and Psoriasis Area and Severity Index (PASI) scores, downregulation of growth factors (GFs), IL-17 A, and MAPK expression after GlcNAc treatment. In addition, GlcNAc treatment reduced neutrophils, monocyte-dendritic cells (Mo-DC) and conventional T cells (Tcons) while increasing monocyte-macrophages (Mo-Macs) and regulatory T cells (Tregs). GlcNAc treatment also downregulated Plet1 overexpression in psoriatic mouse skin and in vitro, reduced proliferation and apoptosis in IL-17 A stimulated human dermal fibroblasts (HDF), along with IL-17 A and TGF-β mRNA expression. Together, these data suggest that, GlcNAc interferes with downstream mechanisms in IL-17 pathway and downregulating Plet1 expression, presenting a promising strategy for Ps treatment.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2217-2230"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464297","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 Gαq in regulating NLRP3 inflammasome activation.","authors":"Ruixue Kong, Lijun Peng, Honggang Bao, Lulu Sun, Yan Feng, Hua Li, Dashan Wang","doi":"10.1007/s00011-024-01961-x","DOIUrl":"10.1007/s00011-024-01961-x","url":null,"abstract":"<p><strong>Background: </strong>G proteins are a class of important signal transducers in mammalians. G proteins can corpoarated with G proteincoupled receptors (GPCRs) and transmit signals from extracellular stimuli into intracellular response, which will regulate a series of biological functions. G-proteins are heterotrimeric proteins composed of Gα, Gβ, and Gγ subunits. Based on structural and functional similarity of their α-subunits, G proteins are typically grouped into four classes (Gi, Gs, Gq/11, and G12/13). The Gq/11 subfamily consists of Gq, G11, G14, and G15/16 proteins. Gαq is the α-subunit of Gq protein and encoded by GNAQ. Our previous studies revealed that Gαq play an important role in regulating T cell survival and T cell differentiation. Inflammasomes are multiprotein complexes that play a critical role in modulating innate inflammatory response. NLRP3 inflammasome is currently the most extensively studied inflammasome.</p><p><strong>Methods: </strong>We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS).</p><p><strong>Results: </strong>We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS).</p><p><strong>Conclusion: </strong>Our results indicate that Gαq regulates NLRP3 inflammasome activation by modulating mitochondrial ROS production. Our research provides new mechanistic insight into the activation of NLRP3 inflammasome. As it has been proved that NLRP3 inflammasome plays an important role in the pathogenesis many diseases such as Alzheimer's disease, cancer, and inflammatory bowel disease, Gαq might become a novel drug target for these diseases in future.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2249-2261"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499588","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":"Environmental and inflammatory factors influencing concurrent gut and lung inflammation.","authors":"April L Raftery, Céline Pattaroni, Nicola L Harris, Evelyn Tsantikos, Margaret L Hibbs","doi":"10.1007/s00011-024-01953-x","DOIUrl":"10.1007/s00011-024-01953-x","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases that affect the gut and lung respectively and can occur comorbidly.</p><p><strong>Methods: </strong>Using the SHIP-1^-/- model of Crohn's-like ileitis and chronic lung inflammation, the two diseases were co-investigated.</p><p><strong>Results: </strong>Contrary to prior literature, Crohn's-like ileitis was not fully penetrant in SHIP-1^-/- mice, and housing in a specific pathogen-free facility was completely protective. Indeed, ileal tissue from SHIP-1^-/- mice without overt ileitis was similar to control ilea. However, SHIP-1^-/- mice with ileitis exhibited increased granulocytes in ileal tissue together with T cell lymphopenia and they lacked low abundance Bifidobacteria, suggesting this bacterium protects against ileitis. Lung disease, as defined by inflammation in lung washes, emphysema, and lung consolidation, was present in SHIP-1^-/- mice regardless of ileitis phenotype; however, there was a shift in the nature of lung inflammation in animals with ileitis, with increased G-CSF and neutrophils, in addition to type 2 cytokines and eosinophils. Deficiency of G-CSF, which protects against lung disease, protected against the development of ileitis in SHIP-1^-/- mice.</p><p><strong>Conclusions: </strong>These studies have defined environmental, immune, and inflammatory factors that predispose to ileitis, and have identified that comorbid lung disease correlates with a granulocyte signature.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2123-2139"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464295","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":"5-oxoETE promote thrombosis in antiphospholipid syndrome by triggering NETs formation through PLC/PKC/ERK pathway.","authors":"Xiaodong Song, Xufeng Chen, Dong Wang, Jie Bai","doi":"10.1007/s00011-024-01956-8","DOIUrl":"10.1007/s00011-024-01956-8","url":null,"abstract":"<p><strong>Background: </strong>One mechanism by which antiphospholipid syndrome (APS) IgG contribute to thrombotic events in patients with APS is through the potentiation of neutrophil extracellular traps (NETs) release. However, the exact mechanism by which APS IgG induces NETs formation and thrombosis has not been fully elucidated.</p><p><strong>Methods: </strong>We conducted untargeted metabolomics on serum samples from thrombotic APS patients to identify metabolic changes. The effect of 5-oxoETE on NETs formation and oxidative stress was evaluated in vitro by treating neutrophils with various concentrations of 5-oxoETE. The involvement of the PLC/PKC/ERK signaling pathway in 5-oxoETE-induced NETs formation was examined using pharmacological inhibitors. In vivo, we assessed the effects of inhibiting 5-oxoETE synthesis or blocking its receptor (OXE-R) on NETs formation and thrombosis in APS mouse models.</p><p><strong>Results: </strong>Serum metabolomics revealed significantly elevated levels of 5-oxoETE in APS patients. In vitro experiments demonstrated that 5-oxoETE, via OXE-R activation of the PLC/PKC/ERK signaling pathway, increased NETs formation and oxidative stress in a dose-dependent manner. In vivo, inhibiting 5-oxoETE synthesis or OXE-R reduced NETs formation and attenuated venous thrombosis in APS mice models.</p><p><strong>Conclusion: </strong>This study identifies 5-oxoETE as a critical mediator of NET formation and thrombosis in APS. Targeting 5-oxoETE or OXE-R may offer a promising therapeutic approach for thrombotic APS and other NET-associated autoimmune diseases.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2165-2177"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390242","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":"Systemic immune inflammation index with all-cause and cause-specific mortality: a meta-analysis.","authors":"Wei Li, Xiaoning Wang, Houze Diao, Yuting Yang, Liyi Ding, Wenru Huan, Yaozhi Chen, Weiwei Cui","doi":"10.1007/s00011-024-01959-5","DOIUrl":"10.1007/s00011-024-01959-5","url":null,"abstract":"<p><strong>Importance: </strong>Studies have reported an association among systemic immune inflammation index (SII), all-cause and cause-specific mortality, but the results are inconsistent.</p><p><strong>Objective: </strong>To comprehensively explore the association between Systemic Immune Inflammation (SII) and the risk of all-cause mortality, cardiovascular disease (CVD), and cancer mortality.</p><p><strong>Evidence review: </strong>A meta-analysis was conducted by reviewing existing literature. The search encompassed prominent databases including PubMed, Embase, Cochrane, and the Web of Science, with the cutoff date set at March 1, 2024. Furthermore, subgroup analyses and dose-response assessments were undertaken to provide a nuanced exploration of mortality risk factors.</p><p><strong>Findings: </strong>A total of 33 articles were included (427,819 participants). In the study, SII was associated with an increased risk of all-cause mortality (HR = 1.45, 95%CI [1.36,1.54], P < 0.05). SII increased the risk of CVD mortality (HR = 1.44, 95%CI [1.29,1.60], P < 0.05). The Linear independence shows that for every 100 units increase in SII, the risk of all-cause and CVD death increases by 5% and 6%. SII was not associated with a statistically significant risk of cancer death (HR = 1.09, 95%CI [0.96,1.23], P < 0.05).</p><p><strong>Conclusions and relevance: </strong>Meta-analysis showed that SII was associated with all-cause mortality and CVD mortality. More data and basic research are needed to confirm the association.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2199-2216"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464298","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-1 receptor antagonist: etiological and drug delivery systems overview.","authors":"Anand Ubhe","doi":"10.1007/s00011-024-01960-y","DOIUrl":"10.1007/s00011-024-01960-y","url":null,"abstract":"<p><strong>Objective: </strong>This article is aims to provide an overview of studies reported in the literature to investigate the etiological role of IL-1/IL-1ra in various disease conditions and the different drug delivery systems developed to achieve IL-1ra as a possible therapeutic option.</p><p><strong>Methods: </strong>Studies reported in PubMed, Google scholar, and other open-source literature related to etiological involvement of IL-1ra in pathophysiological conditions and various drug delivery schemes developed for IL-1ra for its efficacy evaluation as a possible treatment for different disease conditions were surveyed.</p><p><strong>Results and conclusions: </strong>The pathophysiological conditions involving IL-1/IL-1 ra spanned CNS-related disorders, Diabetes, Cardiac disorders, Ocular disease conditions, Gastrointestinal conditions, Tumor growth & metastasis, and miscellaneous conditions. The drug delivery systems developed for IL-1ra included a commercial drug product, Gene therapy, Antibody fusions, Extended-release delivery systems, and Pegylated-IL-1ra systems.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2231-2247"},"PeriodicalIF":4.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499585","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":"Treatment with lipoxin A₄ improves influenza A infection outcome, induces macrophage reprogramming, anti-inflammatory and pro-resolutive responses.","authors":"Flavia Rago, Eliza Mathias Melo, Leigh M Miller, Alexis M Duray, Franciel Batista Felix, Juliana Priscila Vago, Ana Paula de Faria Gonçalves, Ana Luiza Pessoa Mendonça Angelo, Geovanni D Cassali, Monica de Gaetano, Eoin Brennan, Benjamin Owen, Patrick Guiry, Catherine Godson, John F Alcorn, Mauro Martins Teixeira","doi":"10.1007/s00011-024-01939-9","DOIUrl":"10.1007/s00011-024-01939-9","url":null,"abstract":"<p><strong>Introduction: </strong>Influenza A is a virus from the Orthomixoviridae family responsible for high lethality rates and morbidity, despite clinically proven vaccination strategies and some anti-viral therapies. The eicosanoid Lipoxin A4 (LXA4) promotes the resolution of inflammation by decreasing cell recruitment and pro-inflammatory cytokines release, but also for inducing activation of apoptosis, efferocytosis, and macrophage reprogramming.</p><p><strong>Objective: </strong>Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model.</p><p><strong>Method: </strong>Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 μg/kg/day, i.p.) at day 3 post-infection.</p><p><strong>Results: </strong>AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in fpr2/3 ^-/- animals. In mice treated with LXA₄ (50 μg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of T helper 2 cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice.</p><p><strong>Conclusion: </strong>Therefore, treatment with a lipoxin A₄ analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1903-1918"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106953","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":"Cynarin inhibits microglia-induced pyroptosis and neuroinflammation via Nrf2/ROS/NLRP3 axis after spinal cord injury.","authors":"Bin Zhang, Jiasheng Yu, Lei Bao, Dongqian Feng, Yong Qin, Daobo Fan, Xin Hong, Yongyi Chen","doi":"10.1007/s00011-024-01945-x","DOIUrl":"10.1007/s00011-024-01945-x","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy.</p><p><strong>Methods: </strong>Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and pyroptosis to promote neurological recovery after SCI.</p><p><strong>Results: </strong>Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of reactive oxygen species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial pyroptosis and neuroinflammation.</p><p><strong>Conclusions: </strong>To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 inhibitor for microglia in neuropathies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1981-1994"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345963","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":"Trained immunity of synovial macrophages is associated with exacerbated joint inflammation and damage after Staphylococcus aureus infection.","authors":"Peter Silva Rocha, Adryan Aparecido Silva, Celso Martins Queiroz-Junior, Amanda Dias Braga, Thaiane Pinto Moreira, Mauro Martins Teixeira, Flávio Almeida Amaral","doi":"10.1007/s00011-024-01946-w","DOIUrl":"10.1007/s00011-024-01946-w","url":null,"abstract":"<p><strong>Objectives: </strong>Investigate whether and which synoviocytes would acquire trained immunity characteristics that could exacerbate joint inflammation following a secondary Staphylococcus aureus infection.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS) and S. aureus were separately or double injected (21 days of interval) into the tibiofemoral joint cavity of male C57BL/6 mice. At different time points after these stimulations, mechanical nociception was analyzed followed by the analysis of signs of inflammation and damage in the affected joints. The trained immunity markers, including the glycolytic and mTOR pathway, were analyzed in whole tissue or isolated synoviocytes. A group of mice was treated with Rapamycin, an mTOR inhibitor before LPS or S. aureus stimulation.</p><p><strong>Results: </strong>The double LPS - S. aureus hit promoted intense joint inflammation and damage compared to single joint stimulation, including markers in synoviocyte activation, production of proinflammatory cytokines, persistent nociception, and bone damage, despite not reducing the bacterial clearance. The double LPS - S. aureus hit joints increased the synovial macrophage population expressing CX3CR1 alongside triggering established epigenetic modifications associated with trained immunity events in these cells, such as the upregulation of the mTOR signaling pathway (p-mTOR and HIF1α) and the trimethylation of histone H3. Mice treated with Rapamycin presented reduced CX3CR1⁺ macrophage activation, joint inflammation, and bone damage.</p><p><strong>Conclusions: </strong>There is a trained immunity phenotype in CX3CR1⁺ synovial macrophages that contributes to the exacerbation of joint inflammation and damage during septic arthritis caused by S. aureus.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1995-2008"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345967","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":"Gastrin-releasing peptide receptor antagonist RC-3095 inhibits Porphyromonas gingivalis lipopolysaccharide-accelerated atherosclerosis by suppressing inflammatory responses in endothelial cells and macrophages.","authors":"Hyun-Joo Park, Mi-Kyoung Kim, Yeon Kim, Hyung Joon Kim, Hae Ryoun Park, Soo-Kyung Bae, Moon-Kyoung Bae","doi":"10.1007/s00011-024-01934-0","DOIUrl":"10.1007/s00011-024-01934-0","url":null,"abstract":"<p><strong>Objective: </strong>Porphyromonas gingivalis (P. gingivalis), one of the major periodontopathogens, is associated with the progression and exacerbation of atherosclerosis. In this study, we aimed to investigate whether the gastrin-releasing peptide receptor antagonist, RC-3095, could attenuate P. gingivalis LPS-induced inflammatory responses in endothelial cells and macrophages, as well as atherosclerosis in an ApoE^-/- mouse model treated with P. gingivalis LPS.</p><p><strong>Methods: </strong>The effect of RC-3095 on P. gingivalis LPS-induced endothelial inflammation was examined using HUVECs and rat aortic endothelium. THP-1 cells were polarized into M1 macrophages by exposure to P. gingivalis LPS, with or without RC-3095. The effect of RC-3095 on atherosclerosis progression was assessed in high-fat-fed male ApoE^-/- mice through injections of P. gingivalis LPS, RC-3095, or a combination of both.</p><p><strong>Results: </strong>RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells and aortic endothelium by suppressing NF-κB-dependent expressions of ICAM-1 and VCAM-1. In addition, RC-3095 inhibited the P. gingivalis LPS-induced polarization of M1 macrophages by blocking the MAPK and NF-κB signaling pathways. Moreover, RC-3095 decreased the area of atherosclerotic lesions in ApoE^-/- mice, which was accelerated by P. gingivalis LPS injection, and lowered the expressions of ICAM-1 and VCAM-1 in the aortic tissue of mice with atherosclerosis.</p><p><strong>Conclusions: </strong>RC-3095 can alleviate P. gingivalis LPS-induced endothelial inflammation, macrophage polarization, and atherosclerosis progression, suggesting its potential as a therapeutic approach for periodontal pathogen-associated atherosclerosis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1833-1846"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008763","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}