Journal of Immunology Research最新文献

{"title":"The Macrophage Activator GcMAF-RF Enhances the Antitumor Effect of Karanahan Technology through Induction of M2–M1 Macrophage Reprogramming","authors":"Vera S. Ruzanova, Svetlana S. Kirikovich, Evgeniy V. Levites, Anastasia S. Proskurina, Evgeniya V. Dolgova, Genrikh S. Ritter, Yaroslav R. Efremov, Tatyana D. Dubatolova, Alexander V. Sysoev, Danil I. Koleno, Alexandr A. Ostanin, Elena R. Chernykh, Sergey S. Bogachev","doi":"10.1155/2024/7484490","DOIUrl":"https://doi.org/10.1155/2024/7484490","url":null,"abstract":"Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"55 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010068","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":"Assessing the Causal Relationship between Genetically Determined Inflammatory Cytokines and Parkinson’s Disease Risk: A Bidirectional Two-Sample Mendelian Randomization Study","authors":"Hua Xue, Qian Luo, Jiajia Chen, Wenhui Fan","doi":"10.1155/2024/9069870","DOIUrl":"https://doi.org/10.1155/2024/9069870","url":null,"abstract":"<i>Background</i>. Observational studies have suggested an association between inflammatory cytokines and Parkinson’s disease (PD). This Mendelian randomization (MR) was conducted to further assess the causal correlations between inflammatory cytokines and PD. <i>Methods</i>. Genetic instruments associated with inflammatory cytokines were extracted from a large summary genome-wide association studies (GWAS) involving 8,293 European participants. Summary-level statistics for PD were obtained from a large-sample GWAS containing 17 studies that involved European participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted (IVW) method. <i>Results</i>. The IVW method indicated that basic fibroblast growth factor (FGFBasic), interleukin-2 (IL-2), and macrophage migration inhibitory factor (MIF) may be suggestively associated with the risk of PD (OR: 0.71, 95%CI: 0.52–0.96, <i>P</i> = 0.027; OR: 1.18, 95%CI: 1.01–1.38, <i>P</i> = 0.041; and OR: 1.23, 95%CI: 1.04–1.46, <i>P</i> = 0.018). In the reverse direction, monokine induced by interferon gamma (MIG), beta nerve growth factor (bNGF), interleukin-17 (IL-17), and interferon gamma (IFNg) are suggested to be the consequences of PD. <i>Conclusion</i>. Our MR analysis indicated that suggestive associations between circulating levels of FGFBasic, IL-2, and MIF and PD risk. In addition, MIG, bNGF, IL-17, and IFNg are more likely to be involved in the development of downstream PD.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010065","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":"Elotuzumab Enhances CD16-Independent NK Cell-Mediated Cytotoxicity against Myeloma Cells by Upregulating Several NK Cell-Enhancing Genes","authors":"Yan-Hua Wang, Shotaro Hagiwara, Hiroshi Kazama, Yuki Iizuka, Norina Tanaka, Junji Tanaka","doi":"10.1155/2024/1429879","DOIUrl":"https://doi.org/10.1155/2024/1429879","url":null,"abstract":"Multiple myeloma (MM) is an intractable hematological malignancy caused by abnormalities in plasma cells. Combination therapy using antibodies and natural killer (NK) effectors, which are innate immune cells with safe and potent antitumor activity, is a promising approach for cancer immunotherapy and can enhance antitumor effects. Elotuzumab (Elo) is an immune-stimulatory antibody that targets the signaling lymphocytic activation molecule family 7 (SLAMF7) expressed on the surface of MM and NK cells. We confirmed that Elo strongly promoted NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against SLAMF7-positive MM cells in a CD16-dependent NK cell line, and also activated expanded NK cells derived from peripheral blood mononuclear cells of healthy donors and patients with MM in the present study. However, the antitumor effects and genes involved in the direct promotion of NK cell-mediated activation using Elo in CD16-independent NK cells are not clearly known. In this study, we demonstrated that Elo pretreatment significantly enhanced CD16-independent NK cell-mediated cytotoxicity in both SLAMF7-positive MM.1S and SLAMF7-negative K562, U266, and RPMI 8226 tumor cells. Upon direct simulation of CD16-independent NK cells with Elo, increased levels of CD107a degranulation and IFN-<i>γ</i> secretion were observed along with the upregulation of granzyme B, TNF-<i>α</i>, and IL-1<i>α</i> gene expression. The enhanced NK cell function could also be attributed to the increased expression of the transcription factors T-BET and EOMES. Furthermore, the augmentation of the antitumor effects of CD16-independent NK cells upon pretreatment with Elo enhanced the expression of CRTAM, TNFRSF9, EAT-2, and FOXP3 genes and reduced the expression of HSPA6. Our results suggest that Elo directly promotes the cytotoxic function of CD16-independent NK cells against target cells, which is associated with the upregulation of the expression of several NK cell-enhancing genes.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977515","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":"Inhibition of Oxidative Stress-Induced Ferroptosis Can Alleviate Rheumatoid Arthritis in Human","authors":"Yang Liu, Jiang Liang, Zongge Sha, Changfu Yang","doi":"10.1155/2024/9943747","DOIUrl":"https://doi.org/10.1155/2024/9943747","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968873","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":"KIF26B and CREB3L1 Derived from Immunoscore Could Inhibit the Progression of Ovarian Cancer","authors":"Shanshan Cong, Yao Fu, Xibo Zhao, Qiuyan Guo, Tian Liang, Di Wu, Jing Wang, Guangmei Zhang","doi":"10.1155/2024/4817924","DOIUrl":"https://doi.org/10.1155/2024/4817924","url":null,"abstract":"<i>Background</i>. Ovarian cancer (OV) is characteristic of high incidence rate and fatality rate in the malignant tumors of female reproductive system. Researches on pathogenesis and therapeutic targets for OV need to be continued. This study mainly analyzed the immune-related pathogenesis and discovered the key immunotherapy targets for OV. <i>Methods</i>. WGCNA was used for excavating hub gene modules and hub genes related to the immunity of OV. Enrichment analysis was aimed to analyze the related pathways of hub gene modules. Biological experiments were used for exploring the effect of hub genes on SKOV3 cells. <i>Results</i>. We identified two hub gene modules related to the immunoscore of OV and found that these genes in the modules were related to the extracellular matrix and viral infections. At the same time, we also discovered six hub genes related to the immunity of OV. Among them, KIF26B and CREB3L1 can affect the proliferation, migration, and invasion of SKOV3 cells by the Wnt/<i>β</i>-catenin pathway. <i>Conclusions</i>. The local infection or inflammation of ovarian may affect the immunity of OV. KIF26B and CREB3L1 are expected to be potential targets for the immunotherapy of OV.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"1 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765681","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":"Seroprevalence and Potential Risk Factors of Toxocariasis among General Population in Southwest Iran: Implications on the One Health Approach","authors":"Masoud Foroutan, Aida Vafae Eslahi, Shahrzad Soltani, Naser Kamyari, Ehsan Moradi-Joo, Jean-Francois Magnaval, Milad Badri","doi":"10.1155/2024/4246781","DOIUrl":"https://doi.org/10.1155/2024/4246781","url":null,"abstract":"Toxocariasis is one of the most common zoonotic diseases distributed worldwide. This study aimed to estimate the seroprevalence of anti-&lt;i&gt;Toxocara&lt;/i&gt; immunoglobulin G (IgG) antibodies and the associated risk factors among general populations living in urban and rural areas of Abadan and Khorramshahr cities in Khuzestan Province, Southwest Iran. This cross-sectional study was conducted between March and September 2022. There were 363 participants (190 females and 173 males) aged from &lt;20 to ≥60 years old. Anti-&lt;i&gt;Toxocara&lt;/i&gt; IgG antibodies in serum samples were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). A structured questionnaire was employed to collect information regarding sociodemographic status and probable risk factors associated with toxocariasis. It was found that the seroprevalence rate in males (15.0%, 95% CI = 10.47–21.11) was higher than in females (10.5%, 95% CI = 6.92–15.70). Moreover, we observed that the seroprevalence was higher in participants at younger ages compared to other age ranges (COR = 2.55, 95% CI = 0.92–7.12, &lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 21.148 11.7782\" width=\"21.148pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,13.517,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"24.730183800000002 -8.34882 28.185 11.7782\" width=\"28.185pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,24.78,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.02,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,33.984,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,40.224,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,46.466,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;).&lt;/span&gt;&lt;/span&gt; The findings of the univariate analysis revealed that residency in rural areas (&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 21.148 11.7782\" width=\"21.148pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-113\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,13.517,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"24.730183800000002 -8.34882 28.185 11.7782\" width=\"28.185pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,24.78,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.02,0)\"&gt;&lt;use xlink:href=\"#g113-47\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,33.984,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,40.224,0)\"&gt;","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"17 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765767","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":"Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors","authors":"Rodrigo T. Camacho-Pacheco, Jessica Hernández-Pineda, Yesenia Brito-Pérez, Noemi Plazola-Camacho, Irma A. Coronado-Zarco, Gabriela Arreola-Ramírez, Mextli Y. Bermejo-Haro, M. Angel Najera-Hernández, Gabriela González-Pérez, Alma Herrera-Salazar, Andrea Olmos-Ortiz, Diana Soriano-Becerril, Claudia Sandoval-Montes, Ricardo Figueroa-Damian, Sandra Rodríguez-Martínez, Ismael Mancilla-Herrera","doi":"10.1155/2024/8815767","DOIUrl":"https://doi.org/10.1155/2024/8815767","url":null,"abstract":"Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%–42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"5 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765680","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":"Upper Airway Epithelial Tissue Transcriptome Analysis Reveals Immune Signatures Associated with COVID-19 Severity in Ghanaians","authors":"John Demby Sandi, Joshua I. Levy, Kesego Tapela, Mark Zeller, Joshua Afari Yeboah, Daniel Frimpong Saka, Donald S. Grant, Gordon A. Awandare, Peter K. Quashie, Kristian G. Andersen, Lily Paemka","doi":"10.1155/2024/6668017","DOIUrl":"https://doi.org/10.1155/2024/6668017","url":null,"abstract":"The immunological signatures driving the severity of coronavirus disease 19 (COVID-19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected Ghanaians with mild and severe COVID-19, as well as healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with immune suppression, overexpression of proinflammatory cytokines, including <i>CRNN</i>, <i>IL1A</i>, <i>S100A7</i>, and <i>IL23A</i>, and activation of pathways involved in keratinocyte proliferation. <i>SAMD9L</i> was among the differentially regulated interferon-stimulated genes in our mild and severe disease cohorts, suggesting that it may play a critical role in SARS-CoV-2 pathogenesis. By comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530), an elevated expression of antiviral response-related genes was noted in COVID-19-infected Ghanaians. Overall, the study describes immune signatures driving COVID-19 severity in Ghanaians and identifies immune drivers that could serve as potential prognostic markers for future outbreaks or pandemics. It further provides important preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans, which could be contributing to the differences in disease outcomes. Further studies using larger datasets from different populations will expand on these findings.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"41 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765752","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":"RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages","authors":"María José Romero de Ávila, Susana López-López, Aarón García-Blázquez, Almudena Ruiz-García, María Julia González-Gómez, María Luisa Nueda, Victoriano Baladrón, Ignacio Pérez-Roger, Enric Poch, Begoña Ballester-Lurbe, José Javier García-Ramírez, Eva M. Monsalve, María José M. Díaz-Guerra","doi":"10.1155/2024/2264799","DOIUrl":"https://doi.org/10.1155/2024/2264799","url":null,"abstract":"Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-<i>γ</i>. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NF<i>κ</i>B and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as <i>Tnf</i>-<i>α</i>, <i>Irf-1</i>, or <i>Cxcl-10</i>. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"11 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662023","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":"Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses","authors":"Yuehong Chen, Yali Ye, Huan Liu, Zhongling Luo, Qianwei Li, Qibing Xie","doi":"10.1155/2024/6631033","DOIUrl":"https://doi.org/10.1155/2024/6631033","url":null,"abstract":"This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case–control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel–Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 − 0.93, &lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;),&lt;/span&gt;&lt;/span&gt; dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, &lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-113\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"&gt;&lt;use xlink:href=\"#g117-34\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 28.184 11.7782\" width=\"28.184pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"&gt;&lt;use xlink:href=\"#g113-47\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;),&lt;/span&gt;&lt;/span&gt; homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, &lt;span&gt;","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"32 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646294","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}