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Circulating inflammatory markers predict depressive symptomatology in COVID-19 survivors.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-18 DOI: 10.1016/j.cyto.2024.156839
Mariagrazia Palladini, Mario Gennaro Mazza, Rebecca De Lorenzo, Sara Spadini, Veronica Aggio, Margherita Bessi, Federico Calesella, Beatrice Bravi, Patrizia Rovere-Querini, Francesco Benedetti
{"title":"Circulating inflammatory markers predict depressive symptomatology in COVID-19 survivors.","authors":"Mariagrazia Palladini, Mario Gennaro Mazza, Rebecca De Lorenzo, Sara Spadini, Veronica Aggio, Margherita Bessi, Federico Calesella, Beatrice Bravi, Patrizia Rovere-Querini, Francesco Benedetti","doi":"10.1016/j.cyto.2024.156839","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156839","url":null,"abstract":"<p><p>Growing evidence suggests the neurobiological mechanism upholding post-COVID-19 depression mainly relates to immune response and subsequent unresolved low-grade inflammation. Herein we exploit a broad panel of cytokines serum levels measured in COVID-19 survivors at one- and three-month since infection to predict post-COVID-19 depression. 87 COVID survivors were screened for depressive symptomatology at one- and three-month after discharge through the Beck Depression Inventory (BDI-13) and the Zung Self-Rating Depression Scale (ZSDS) at San Raffaele Hospital. Blood samples were collected at both timepoints and analyzed through Luminex. We entered one-month 42 inflammatory compounds into two separate penalized logistic regression models to evaluate their reliability in identifying COVID-19 survivors suffering from clinical depression at the two timepoints, applied within a machine learning routine. Delta values of analytes lowering between timepoints were entered in a third model predicting presence long-term depression. 5000 bootstraps were computed to determine significance of predictors. The cross-sectional model reached a balance accuracy (BA) of 76 % and a sensitivity of 70 %. Post-COVID-19 depression was predicted by high levels of CCL17, CCL22. On the other hand, CXCL10, CCL2, CCL3, CCL8, CXCL5, CCL15, CCL23, CXCL13, and GM-CSF showed protective effects. The longitudinal model obtained good performance as well (BA = 74 % and sensitivity = 68 %), revealing CXCL16 and CCL25 as additional drivers of clinical depression. Moreover, dynamic changes of analytes over time accurately predicted long-term depression (BA = 76 % and sensitivity = 75 %). Our findings unveil a putative immune profile upholding post-COVID-19 depression, thus reinforcing the need to deepen molecular mechanisms to appropriately target depression.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156839"},"PeriodicalIF":3.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862591","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}
引用次数: 0
Akkermansia muciniphila activates natural killer cells by suppressing the TGF-β signaling pathway in lung adenocarcinoma cells.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-18 DOI: 10.1016/j.cyto.2024.156833
Yong Li, Huiqin Huang, Hang Xie, Rongxiang Cao, Xiuling Li, Feijian Huang, Lu Lin, Limin Chen
{"title":"Akkermansia muciniphila activates natural killer cells by suppressing the TGF-β signaling pathway in lung adenocarcinoma cells.","authors":"Yong Li, Huiqin Huang, Hang Xie, Rongxiang Cao, Xiuling Li, Feijian Huang, Lu Lin, Limin Chen","doi":"10.1016/j.cyto.2024.156833","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156833","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) stands out as a prevalent malignant tumor necessitating innovative strategies to enhance therapeutic outcomes. Akkermansia muciniphila (AKK) has emerged as intricately linked to tumor immunotherapy, yet its impact on natural killer (NK) cells, which play a crucial role in immunotherapy, remains unclear. This study aims to investigate the effects of AKK outer membrane proteins on NK cells in LUAD and elucidate potential associated molecular mechanisms. 16S rRNA sequencing was employed to analyze bacterial genera and their abundance in fecal samples from LUAD patients. Co-culturing of NK-92 cells with LUAD cells, with or without treatment of AKK outer membrane protein Amuc_1100, was conducted to investigate the mechanisms of AKK on LUAD. Additionally, a xenograft mouse model was established to validate the effects of AKK in an in vivo setting. The experimental findings indicated that LUAD patients with elevated AKK levels in their fecal samples demonstrated increased NK cell infiltration and reduced TGF-β levels. Treatment with Amuc_1100 elevated TNF-α and IL-15 cytokine levels, decreased TGF-β levels and proteins associated with TGF-β pathway, enhanced NK cell cytotoxicity, upregulated perforin and granzyme B expression, induced apoptosis and cell cycle arrest, thereby inhibiting cancer cell proliferation. Amuc_1100 also impeded tumor growth in vivo. In summary, these results suggest that AKK activates NK cells to target tumor cells by suppressing the TGF-β signaling pathway in LUAD cells, underscoring the potential of Akk as an effective immunotherapeutic agent in LUAD NK cell-directed therapies.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156833"},"PeriodicalIF":3.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862590","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}
引用次数: 0
The possible anti-tumor effects of regulatory T cells plasticity / IL-35 in the tumor microenvironment of the major three cancer types.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-17 DOI: 10.1016/j.cyto.2024.156834
Rehab G Khalil, Dina A Mohammed, Hadeer M Hamdalla, Osama M Ahmed
{"title":"The possible anti-tumor effects of regulatory T cells plasticity / IL-35 in the tumor microenvironment of the major three cancer types.","authors":"Rehab G Khalil, Dina A Mohammed, Hadeer M Hamdalla, Osama M Ahmed","doi":"10.1016/j.cyto.2024.156834","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156834","url":null,"abstract":"<p><p>T lymphocytes are among the immunological cells that make up the tumor microenvironment (TME), and they are essential in the growth of tumors and anti-tumor reactions. Regulatory T cells (Treg cells) are a subset of CD4+ T cells in the immune system that suppress the immune system. They are distinguished by their expression of the master transcription factor forkhead box protein P3 (FOXP3). Furthermore, Treg cells are essential for maintaining immunological homeostasis, inhibiting inflammation, and maintaining self-tolerance. In a variety of malignancies within the TME, Treg cells demonstrate notable flexibility and functional diversity. Highly plastic Treg cells can change into Th-like Treg cells in specific circumstances, which allow them to secrete particular pro-inflammatory cytokines. Interleukin 35 (IL-35) is a part of the immunosuppressive cytokines that belong to the IL-12 family. Treg cells release IL-35, which was elevated in the peripheral blood and TME of numerous cancer patients, implying that IL-35 in the TME may be an intriguing target for cancer therapy. In cancer, IL-35 is a two-edged sword; it promotes tumorigenicity in cancer cells while shielding them from apoptosis. Nonetheless, other investigations have mentioned its conflicting effects on cancer prevention. Herein, we provide an updated understanding of the critical mechanisms behind the anticancer immunity mediated by Treg cells plasticity, the role of IL-35, and tactics to strengthen the immune response against malignancies, outlining major clinical trials that used Treg cells/IL-35 therapies in the three main cancer types (lung, breast, and colorectal cancers).</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156834"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851834","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}
引用次数: 0
Interferon therapy in alpha and Delta variants of SARS-CoV-2: The dichotomy between laboratory success and clinical realities.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-17 DOI: 10.1016/j.cyto.2024.156829
Atefe Alirezaee, Milad Mirmoghtadaei, Hanieh Heydarlou, Asiye Akbarian, Zahra Alizadeh
{"title":"Interferon therapy in alpha and Delta variants of SARS-CoV-2: The dichotomy between laboratory success and clinical realities.","authors":"Atefe Alirezaee, Milad Mirmoghtadaei, Hanieh Heydarlou, Asiye Akbarian, Zahra Alizadeh","doi":"10.1016/j.cyto.2024.156829","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156829","url":null,"abstract":"<p><p>The COVID-19 pandemic has caused significant morbidity and mortality worldwide. The emergence of the Alpha and Delta variants of SARS-CoV-2 has led to a renewed interest in using interferon therapy as a potential treatment option. Interferons are a group of signaling proteins produced by host cells in response to viral infections. They play a critical role in the innate immune response to viral infections by inducing an antiviral state in infected and neighboring cells. Interferon therapy has shown promise as a potential treatment option for COVID-19. In this review paper, we review the current knowledge regarding interferon therapy in the context of the Alpha and Delta variants of SARS-CoV-2 and discuss the challenges that must be overcome to translate laboratory findings into effective clinical treatments.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156829"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851833","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}
引用次数: 0
The correlation of bisphenol A exposure on inflammatory cytokines in preschool children.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-16 DOI: 10.1016/j.cyto.2024.156835
Wenya Cai, Qingshan Yan, Yuhong Deng, Yong Guo
{"title":"The correlation of bisphenol A exposure on inflammatory cytokines in preschool children.","authors":"Wenya Cai, Qingshan Yan, Yuhong Deng, Yong Guo","doi":"10.1016/j.cyto.2024.156835","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156835","url":null,"abstract":"<p><strong>Objective: </strong>Based on current evidence suggesting that bisphenol A (BPA) may contribute to obesity through the modulation of inflammatory markers, this study aims to investigate the correlation between BPA exposure and cellular inflammatory factors in preschool children.</p><p><strong>Methods: </strong>A total of 155 preschool children aged 4-6 years were included. Urine and blood samples were collected. BPA exposure was detected by liquid chromatography-tandem mass spectrometry through urine samples. The levels of six inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were determined by flow fluorescence technique. The correlation between urinary BPA exposure and cellular inflammatory factors was analyzed using Spearman's correlation and respectively stratified by gender and BMI.</p><p><strong>Results: </strong>The detection rate of BPA in urine samples was 100 %. The median urinary BPA concentration was 0.48 μg/L(IQR:0.25-1.02 μg/L), and the creatinine-adjusted BPA concentration was 0.94 μg/g(IQR:0.57-1.66 μg/g). BPA level was negatively correlated with IL-10 (r = -0.172, P < 0.05). After stratification by gender, the negative association between BPA exposure and IL-10 was found in females (r = -0.257, P < 0.05), while no association was found in males. According to BMI stratification, BPA exposure in overweight/obese children was positively correlated with IL-6 (r = 0.354, P < 0.05).</p><p><strong>Conclusions: </strong>Our study demonstrated that BPA exposure in preschool children was correlated with a decrease in levels of IL-10, and this effect was significantly expressed in girls. In addition, BPA exposure in overweight/obese children was correlated with increased levels of IL-6. However, the mechanism between BPA and inflammatory factors remains to be further explored.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156835"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845449","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}
引用次数: 0
When recombinant proteins go wrong: The hidden pitfall of recombinant protein contamination.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-14 DOI: 10.1016/j.cyto.2024.156830
Lejla Svraka, Hakim Ben Abdallah, Claus Johansen
{"title":"When recombinant proteins go wrong: The hidden pitfall of recombinant protein contamination.","authors":"Lejla Svraka, Hakim Ben Abdallah, Claus Johansen","doi":"10.1016/j.cyto.2024.156830","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156830","url":null,"abstract":"<p><p>Recombinant proteins are critical tools in research; however, their purity is often assumed rather than verified, leading to potential experimental errors. This study aimed to investigate the inflammatory role of recombinant human IL-17F in dermal fibroblasts. Unexpectedly, we discovered with Western blot that recombinant IL-17F from the supplier was contaminated with IL-4, leading to unintended stimulatory effects such as STAT6 phosphorylation and gene induction of CCL26 and IL4R. This contamination led to misinterpretation of data, loss of research time, and erroneous conclusions about IL-17F activity. These findings underscore the critical need for stringent quality control in recombinant protein production and highlight the risks of relying on single-source suppliers. Researchers should remain cautious about potential contamination, ideally validating proteins from multiple suppliers. Our experience illustrates a broader requirement for suppliers to strengthen quality assurance measures, as contaminants can propagate misleading data in the literature and undermine research reproducibility.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156830"},"PeriodicalIF":3.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826895","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}
引用次数: 0
Correlation of IL-10 and IL18 with the development of liver cirrhosis associated with hepatitis B virus infection: A systematic review. IL-10和IL18与乙型肝炎病毒感染相关肝硬化发展的相关性:系统综述。
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-12 DOI: 10.1016/j.cyto.2024.156818
Mohammad Heiat, Mohammad Javanbakht, Davood Jafari, Mohadeseh Poudineh, Fatemeh Heydari, Heidar Sharafi, Seyed Moayed Alavian
{"title":"Correlation of IL-10 and IL18 with the development of liver cirrhosis associated with hepatitis B virus infection: A systematic review.","authors":"Mohammad Heiat, Mohammad Javanbakht, Davood Jafari, Mohadeseh Poudineh, Fatemeh Heydari, Heidar Sharafi, Seyed Moayed Alavian","doi":"10.1016/j.cyto.2024.156818","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156818","url":null,"abstract":"<p><strong>Background: </strong>Patients who have been infected with the Hepatitis B virus (HBV) are susceptible to developing liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The objective of this systematic review was to comprehensively scrutinize the existing evidence concerning the association between host genetic polymorphisms and HBV-associated LC.</p><p><strong>Methods: </strong>We searched databases of PubMed, Scopus, and Web of Science for relevant articles published from building databases to 25 October 2023.</p><p><strong>Result: </strong>We detected 104 relevant articles, relating to 84 individuals genes. Nine genes had the strong evidence of correlation, including IL-10, IL-18, IL-1B, TGF- β, TLR3, STAT4, IL-1RN, Tim3, and IFN receptors. A positive correlation was found for 33 genes but this data had not yet been replicated, 11 genes had limited or mixed evidence of a correlation, and 34 genes indicated no correlation. IL-10 and IL-18 had the most evidence of correlation. There was a notable amount of diversity in both the design and method of studies and data quality.</p><p><strong>Conclusion: </strong>IL-10 and IL-18 had the most evidence of correlation. There was a notable amount of diversity in both the design and method of studies and data quality. It is of necessary to take into account the fundamental mechanism behind these associations and discern those that are confounded by the coexistence of other LC/HCC risk factors and response to therapy. These results are expected to guide future studies on the genetic susceptibility of HBV-related LC/HCC.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156818"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821555","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}
引用次数: 0
Exogenous binding immunoglobulin protein (BiP) enhance immune regulatory phenotype in ex-vivo Mtb infected PBMCs stratified based on QuantiFERON response.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-12 DOI: 10.1016/j.cyto.2024.156832
Bongani Motaung, Candice Snyders, Stephanus Malherbe, Andrea Gutschmidt, Ilana van Rensburg, Andre G Loxton
{"title":"Exogenous binding immunoglobulin protein (BiP) enhance immune regulatory phenotype in ex-vivo Mtb infected PBMCs stratified based on QuantiFERON response.","authors":"Bongani Motaung, Candice Snyders, Stephanus Malherbe, Andrea Gutschmidt, Ilana van Rensburg, Andre G Loxton","doi":"10.1016/j.cyto.2024.156832","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156832","url":null,"abstract":"<p><p>Even though anti-tuberculosis (TB) treatment is readily available, Mycobacterium tuberculosis (Mtb) infection continues to be a global threat with a high death rate recorded from a single infectious agent. This highlights the significance of developing new strategies to curb the growing Mtb infection cases. Host-directed therapies (HDT) offer a promising approach that includes both drug discovery and drug repurposing, aimed at identifying host targets and promoting immune cell populations that can lead to better infection outcomes. In this context, we investigated the potential of exogenous Binding Immunoglobulin Protein (BiP) to induce such changes ex-vivo using PBMCs from healthy (QFN-) and Mtb exposed (QFN+) individuals. We analysed cell surface expression and cytokine profiles across eight different stimulation conditions including human full-length BiP protein (20 μg/ml), TLR-9a (0.5 μM), BiP/TLR-9a combination, isoniazid (1 μM), H37Rv (MOI: 1: 10), and pooled bronchoalveolar lavage (BAL) samples collected at TB diagnosis (TBdx) and at month 6 (M6) of anti-TB treatment. Our results revealed that BiP-stimulated PBMCs showed a significant reduction of interleukin (IL)-10 secretion, along with increased IL-4, IL-5, IL-13, and soluble Fas-L (sFasL) secretion. We also observed that BiP stimulation enhanced the expression of membrane bound Fas-L (CD178) and IL5Ra (CD125) in B-cells isolated from both QFN- and QFN+ groups. Additionally, BiP exhibited a synergistic effect with TLR-9a, further boosting this co-expression. Moreover, we observed that BiP induced IL5Ra expression in both CD3<sup>+</sup>CD5<sup>lo</sup> and CD3<sup>+</sup>CD5<sup>hi</sup> T-cell populations. This study explores the effects of exogenous BiP on cell functionality and provides valuable insights into its potential to modulate host cell responses, which could be explored as a host-directed therapy for TB in the future.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156832"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821556","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}
引用次数: 0
Blood IL-1α and IL-6 predict specific breast cancer-induced increases in hippocampal pro-inflammatory cytokines in mice.
IF 3.7 3区 医学
Cytokine Pub Date : 2024-12-11 DOI: 10.1016/j.cyto.2024.156826
Delyse McCaffrey, Cynthia Shannon Weickert, Adam K Walker
{"title":"Blood IL-1α and IL-6 predict specific breast cancer-induced increases in hippocampal pro-inflammatory cytokines in mice.","authors":"Delyse McCaffrey, Cynthia Shannon Weickert, Adam K Walker","doi":"10.1016/j.cyto.2024.156826","DOIUrl":"https://doi.org/10.1016/j.cyto.2024.156826","url":null,"abstract":"<p><p>Neuroinflammation is a key factor in cognitive and behavioral changes seen in patients with non-CNS cancers, and cytokine levels in the blood are often used as a proxy for brain inflammation. However, this approach has yielded inconsistent results, and a common inflammatory signature remains elusive. To explore whether a blood-to-brain inflammatory signature exists across breast cancer types, we assessed cytokine and glial protein responses in the hippocampus, prefrontal cortex (PFC), and their relationship to serum cytokines in mice bearing three different mammary cancers (n = 40). While cytokine profiles in both serum and brain varied by cancer type, IL-1β and IL-4 were consistently altered across brain regions. In some cases, elevated serum IL-1α and IL-6 correlated with increased hippocampal IL-6. These findings support the use of blood cytokines to identify cancer patients at risk for cognitive and psychiatric comorbidities. However, our data also suggest that relying solely on serum cytokines may lead to under-diagnosis, as some mice exhibited brain cytokine elevations without changes in serum levels. This underscores the need for a broader range of inflammatory markers in blood to better identify at-risk patients. Brain region-specific differences in the cytokine response to mammary cancer highlighted the hippocampus as more vulnerable to cancer-induced inflammation than the PFC. We observed region-specific glial cell reactivity, however, only astrocyte and oligodendrocyte markers were correlated with cytokine changes within the hippocampus. Elevated serum IL-1α and IL-6 were correlated with reduced cortical astrocyte reactivity, suggesting that these cytokines can inform glial cell-specific changes in this region.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"156826"},"PeriodicalIF":3.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816659","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}
引用次数: 0
Messages in CD40L are encrypted for residue-specific functions
IF 3.7 3区 医学
Cytokine Pub Date : 2024-11-30 DOI: 10.1016/j.cyto.2024.156824
Akshata Bammigatti , Soumya Kanti Ghosh , Syamdas Bandyopadhyay , Bhaskar Saha
{"title":"Messages in CD40L are encrypted for residue-specific functions","authors":"Akshata Bammigatti ,&nbsp;Soumya Kanti Ghosh ,&nbsp;Syamdas Bandyopadhyay ,&nbsp;Bhaskar Saha","doi":"10.1016/j.cyto.2024.156824","DOIUrl":"10.1016/j.cyto.2024.156824","url":null,"abstract":"<div><div>CD40-CD40-ligand (CD40L) interaction plays crucial immunoregulatory roles, as CD40 signals through different signaling intermediates to convert the messages from CD40L to effector functions. Being a TNFα receptor family member, CD40 binds TNFα receptor-associated factors, assembles signalosome complexes and decrypts the messages from CD40L through different signaling modules to result in residue-specific effector functions. The evidence for such a residue-specific message encryption first came from the CD40L mutations resulting in X-linked hyper-IgM syndrome, as the extent of effects varied with the residue mutated. The structural studies on the CD40-CD40L interaction implied differential involvement of the interacting residues on CD40L in influencing the effector functions. Three lines of evidence indicate the previously implied residue-specific message encryption in CD40L: screening of a dodecameric peptide library for CD40 binders identified two peptides with different sequences resulting in counteractive effector functions in macrophages; a series of CD40L mutants identified that the mutations in these residues selectively affected CD40 signaling and macrophage effector functions; and, a panel of 40-mer peptides, representing the CD40-interacting domain of mouse CD40L, with single substitutions resulted in altered CD40 signaling through various signaling intermediates and effector functions in mouse macrophages. We therefore construct the first-ever message encryption-decryption in a biological receptor-ligand system wherein the CD40L residues that interact with CD40 residues have encrypted messages, which are decoded by CD40 signaling to result in residue-specific effector functions. This review presents a novel perspective of receptor-ligand interaction as a system of message transmission, message decoding by signaling, and its transcription to various read-outs. [250 words].</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156824"},"PeriodicalIF":3.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745199","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}
引用次数: 0
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