المؤلفون: Ting Sun, Qian Chen, Junchi Mei, Yan Li

المصدر: BMC Psychiatry, Vol 23, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: Major depressive disorder, Estradiol, Soluble glycoprotein 130, Soluble interleukin-6 receptor α, Interleukin-6, Psychiatry, RC435-571

الوصف: Abstract Background It has been hypothesized that the IL-6/sIL-6R/sgp130 complex, an inflammatory complex, plays a critical role in the pathogenesis of major depressive disorder (MDD). Estradiol (E2) is a sex steroid hormone involved in emotional regulation and MDD. This study aimed to investigate the relationship between E2 and IL-6/sIL-6R/sgp130 complex in patients with MDD. Methods Using enzyme-linked immunosorbent assay, the levels of IL-6, sIL-6Rα, and sgp130 were compared between 117 female patients with MDD and 122 healthy controls.The serum concentrations of E2 and other biomarkers were also measured. Results (1) The serum levels of IL-6 and sIL-6Rα in patients with MDD were significantly higher than those in the control group, while the serum levels of sgp130 and E2 were significantly lower (all P

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-244XTest

الوصول الحر: https://doaj.org/article/ce19dd25cb3e4e2ba0aa6e1d54a36cc3Test

المؤلفون: Shu-Hao Hsu, Chung-Feng Ph.D Kao, Hu-Ming M.D Chang, Shih-Chun Meng, Jia-Lin Shi, Ming-Chyi Huang

المصدر: Taiwanese Journal of Psychiatry, Vol 37, Iss 4, Pp 175-181 (2023)

مصطلحات موضوعية: blood interleukin-6, blood soluble interleukin-6 receptor, blood tumor necrosis factor-alpha, neuro-immune dysregulation, Psychiatry, RC435-571

الوصف: Objectives: Alcohol is known to modulate the immune system, which is associated with the pathophysiology of alcohol dependence (AD). Interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), and tumor necrosis factor-alpha (TNF-α) are widely studied immune molecules in neuropsychiatric disorders. In this study, we intended to investigate the differences of blood levels of cytokines between patients with AD during early withdrawal and healthy control (HC). Methods: In this study, we included 85 patients diagnosed with AD according to the DSM-IV criteria and 49 HC participants. Blood samples were collected from the AD group and HC group on the first and seventh days of withdrawal. Blood levels of IL-6, sIL-6R, and TNF-α were measured using the enzyme-linked immunosorbent assay. Results: The baseline blood TNF-α levels in the AD group were significantly higher than those in the HC group (3.0 ± 1.6 pg/mL vs. 1.5 ± 0.9 pg/mL, p < 0.001), while blood sIL-6R levels were significantly lower (153.0 ± 37.0 pg/mL vs. 171.4 ± 39.6 pg/mL, p < 0.01). The baseline blood IL-6 and TNF-α levels were correlated with alcohol consumption amount and duration of AD. After one week of alcohol withdrawal, the blood TNF-α level of the AD group was still higher than that of the control group, whereas the blood IL-6 and IL-6R were normalized. Conclusion: Our findings suggest blood cytokines are dysregulated in patients with AD.

وصف الملف: electronic resource

العلاقة: http://www.e-tjp.org/article.asp?issn=1028-3684;year=2023;volume=37;issue=4;spage=175;epage=181;aulast=HsuTest; https://doaj.org/toc/1028-3684Test; https://doaj.org/toc/2666-2078Test

الوصول الحر: https://doaj.org/article/ea1910d6c33f4c39a858e95df1c9751cTest

المؤلفون: Villar Fincheira, Paulina, Paredes, Aaron J., Hernandez Diaz, Tomas, Norambuena Soto, Ignacio, Cancino Arenas, Nicole, Sanhueza Olivares, Fernanda, Contreras Briceño, Felipe, Mandiola Ovalle, Jorge, Bruneau, Nicole, Garcia, Lorena, Ocaranza, María Paz, Troncoso, Rodrigo, Gabrielli, Luigi, Chiong, Mario

مصطلحات موضوعية: Exercise, Interleukin-6, Runners, Soluble interleukin-6 receptor, Vascular smooth muscle cell, Medicina y salud

الوقت: 610

الوصف: Little is known about the effects of training load on exercise-induced plasma increase of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) and their relationship with vascular remodeling. We sought to evaluate the role of sIL 6R as a regulator of IL-6-induced vascular remodeling. Forty-four male marathon runners were recruited and allocated into two groups: low-training (LT, <100 km/week) and high-training (HT, >= 100 km/week), 22 athletes per group. Twenty-one sedentary participants were used as reference. IL-6, sIL-6R and sgp130 levels were measured in plasma samples obtained before and immediately after finishing a marathon (42.2-km). Aortic diameter was measured by echocardiography. The inhibitory effect of sIL-6R on IL-6-induced VSMC migration was assessed using cultured A7r5 VSMCs. Basal plasma IL-6 and sIL-6R levels were similar among sedentary and athlete groups. Plasma IL-6 and sIL-6R levels were elevated after the marathon, and HT athletes had higher post-race plasma sIL-6R, but not IL-6, level than LT athletes. No changes in sgp130 plasma levels were found in LT and HT groups before and after running the marathon. Athletes had a more dilated ascending aorta and aortic root than sedentary participants with no differences between HT and LT athletes. However, a positive correlation between ascending aorta diameter and plasma IL-6 levels corrected by training load and years of training was observed. IL-6 could be responsible for aorta dilation because IL-6 stimulated VSMC migration in vitro, an effect that is inhibited by sIL-6R. However, IL-6 did not modify cell proliferation, collagen type I and contractile protein of VSMC. Our results suggest that exercise induces vascular remodeling. A possible association with IL-6 is proposed. Because sIL-6R inhibits IL-6-induced VSMC migration, a possible mechanism to regulate IL-6-dependent VSMC migration is also proposed. ; FONDECYT ; FONDAP

وصف الملف: application/pdf

العلاقة: Frontiers in Physiology; MEDLINE:34707507; SCOPUS_ID:85117760625; https://doi.org/10.3389/fphys.2021.722528Test; https://repositorio.uc.cl/handle/11534/80918Test

الإتاحة: https://doi.org/10.3389/fphys.2021.722528Test
https://repositorio.uc.cl/handle/11534/80918Test

المؤلفون: Paulina Villar-Fincheira, Aaron J. Paredes, Tomás Hernández-Díaz, Ignacio Norambuena-Soto, Nicole Cancino-Arenas, Fernanda Sanhueza-Olivares, Felipe Contreras-Briceño, Jorge Mandiola, Nicole Bruneau, Lorena García, María Paz Ocaranza, Rodrigo Troncoso, Luigi Gabrielli, Mario Chiong

المصدر: Frontiers in Physiology, Vol 12 (2021)

مصطلحات موضوعية: interleukin-6, soluble interleukin-6 receptor, vascular smooth muscle cell, runners, exercise, Physiology, QP1-981

الوصف: Little is known about the effects of training load on exercise-induced plasma increase of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) and their relationship with vascular remodeling. We sought to evaluate the role of sIL 6R as a regulator of IL-6-induced vascular remodeling. Forty-four male marathon runners were recruited and allocated into two groups: low-training (LT,

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphys.2021.722528/fullTest; https://doaj.org/toc/1664-042XTest

الوصول الحر: https://doaj.org/article/30591f36357147439c19e17f73b57cffTest

المؤلفون: Yoshihiko Raita, Zhaozhong Zhu, Carlos A. Camargo, Robert J. Freishtat, Debby Ngo, Liming Liang, Kohei Hasegawa

المصدر: Frontiers in Medicine, Vol 8 (2021)

مصطلحات موضوعية: interleukin-6, soluble interleukin-6 receptor, trans-signaling pathway, asthma, Mendelian randomization, GWAS, Medicine (General), R5-920

الوصف: Purpose: Emerging evidence suggests a potential role of interleukin-6 pathways—trans-signaling with soluble interleukin-6 receptors—in the asthma pathobiology. Despite the evidence for their associations with asthma, the causal role of soluble interleukin-6 receptors remains uncertain. We investigated the relations of soluble interleukin-6 receptors with asthma and its major phenotypes.Methods: We conducted a two-sample Mendelian randomization study. As genetic instruments, we selected 33 independent cis-acting variants strongly associated with the level of plasma soluble interleukin-6 receptor in the INTERVAL study. To investigate the association of variants with asthma and its phenotypes, we used genome-wide association study data from the UK Biobank. We combined variant-specific causal estimates by the inverse-variance weighted method for each outcome.Results: Genetically-instrumented soluble interleukin-6 receptor level was associated with a significantly higher risk of overall asthma (OR per one standard deviation increment in inverse-rank normalized soluble interleukin-6 receptor level, 1.02; 95%CI, 1.01–1.03; P = 0.004). Sensitivity analyses demonstrated consistent results and indicated no directional pleiotropy—e.g., MR-Egger (OR, 1.03; 95%CI, 1.01–1.05; P = 0.002; Pintercept =0.37). In the stratified analysis, the significant association persisted across asthma phenotypes—e.g., childhood asthma (OR, 1.05; 95%CI, 1.02–1.08; P < 0.001) and obese asthma (OR, 1.02; 95%CI 1.01–1.03; P = 0.007). Sensitivity analysis using 16 variants selected with different thresholds also demonstrated significant associations with overall asthma and its phenotypes.Conclusion: Genetically-instrumented soluble interleukin-6 receptor level was causally associated with modestly but significantly higher risks of asthma and its phenotypes. Our observations support further investigations into identifying specific endotypes in which interleukin-6 pathways may play major roles.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2021.665057/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/96404f26f9604915ada0e8ecb7e1454aTest

المؤلفون: Kelly, Kristen M., Smith, Jennifer A., Mezuk, Briana

المصدر: Kelly , K M , Smith , J A & Mezuk , B 2021 , ' Depression and interleukin-6 signaling : A Mendelian Randomization study ' , Brain, Behavior, and Immunity , vol. 95 , pp. 106-114 . https://doi.org/10.1016/j.bbi.2021.02.019Test

مصطلحات موضوعية: Depression, Inflammation, Interleukin-6, Mendelian Randomization, sIL-6R, Soluble interleukin-6 receptor, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being

الوصف: Background: A large body of research has reported associations between depression and elevated interleukin-6 (IL-6), a cytokine with several roles including pro-inflammatory signaling. The nature and directionality of this relationship are not yet clear. In this study we use Mendelian Randomization to examine the possibility of a causal relationship between IL-6 and depressive symptoms, and to explore multiple signaling pathways that could serve as mechanisms for this relationship. Methods: This study uses a two-sample Mendelian Randomization design. Data come from the UK Biobank (n = 89,119) and published summary statistics from six existing GWAS analyses. The primary analysis focuses on the soluble interleukin-6 receptor (sIL-6R), which is involved in multiple signaling pathways. Exploratory analyses use C-reactive protein (CRP) and soluble glycoprotein 130 (sgp130) to further examine potential underlying mechanisms. Results: Results are consistent with a causal effect of sIL-6R on depression (PCA-IVW Odds Ratio: 1.023 (95% Confidence Interval: 1.006–1.039), p = 0.006). Exploratory analyses demonstrate that the relationship could be consistent with either decreased classical signaling or increased trans signaling as the underlying mechanism. Discussion: These results strengthen the body evidence implicating IL-6 signaling in depression. When compared with existing observational and animal findings, the direction of these results suggests involvement of IL-6 trans signaling. Further study is needed to examine whether IL6R genetic variants might influence IL-6 trans signaling in the brain, as well as to explore other potential pathways linking depression and inflammation.

العلاقة: https://research.vu.nl/en/publications/87d3955d-3b14-414e-87a2-2a92491a4b66Test

الإتاحة: https://doi.org/10.1016/j.bbi.2021.02.019Test
https://research.vu.nl/en/publications/87d3955d-3b14-414e-87a2-2a92491a4b66Test
https://hdl.handle.net/1871.1/87d3955d-3b14-414e-87a2-2a92491a4b66Test
http://www.scopus.com/inward/record.url?scp=85105464834&partnerID=8YFLogxKTest
http://www.scopus.com/inward/citedby.url?scp=85105464834&partnerID=8YFLogxKTest

المؤلفون: Villar Fincheira, Paulina Fernanda, Paredes, Aaron J., Hernández Díaz, Tomás Alonso, Norambuena Soto, Ignacio Esteban, Cancino Arenas, Nicole Ester, Sanhueza Olivares, Fernanda, Contreras Briceño, Felipe, Mandiola, Jorge, Bruneau Leyton, Nicole Nayira, García Nannig, Lorena, Ocaranza, María Paz, Troncoso Cotal, Rodrigo Hernán, Gabrielli, Luigi, Chiong Lay, Mario Martin

المصدر: Frontiers in Physiology

مصطلحات موضوعية: Interleukin-6, Soluble interleukin-6 receptor, Vascular smooth muscle cell, Runners, Exercise

الوصف: Little is known about the effects of training load on exercise-induced plasma increase of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) and their relationship with vascular remodeling. We sought to evaluate the role of sIL 6R as a regulator of IL-6-induced vascular remodeling. Forty-four male marathon runners were recruited and allocated into two groups: low-training (LT, <100 km/week) and high-training (HT, >= 100 km/week), 22 athletes per group. Twenty-one sedentary participants were used as reference. IL-6, sIL-6R and sgp130 levels were measured in plasma samples obtained before and immediately after finishing a marathon (42.2-km). Aortic diameter was measured by echocardiography. The inhibitory effect of sIL-6R on IL-6-induced VSMC migration was assessed using cultured A7r5 VSMCs. Basal plasma IL-6 and sIL-6R levels were similar among sedentary and athlete groups. Plasma IL-6 and sIL-6R levels were elevated after the marathon, and HT athletes had higher post-race plasma sIL-6R, but not IL-6, level than LT athletes. No changes in sgp130 plasma levels were found in LT and HT groups before and after running the marathon. Athletes had a more dilated ascending aorta and aortic root than sedentary participants with no differences between HT and LT athletes. However, a positive correlation between ascending aorta diameter and plasma IL-6 levels corrected by training load and years of training was observed. IL-6 could be responsible for aorta dilation because IL-6 stimulated VSMC migration in vitro, an effect that is inhibited by sIL-6R. However, IL-6 did not modify cell proliferation, collagen type I and contractile protein of VSMC. Our results suggest that exercise induces vascular remodeling. A possible association with IL-6 is proposed. Because sIL-6R inhibits IL-6-induced VSMC migration, a possible mechanism to regulate IL-6-dependent VSMC migration is also proposed. ; Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1170963 Comision Nacional de ...

وصف الملف: application/pdf

العلاقة: Frontiers in Physiology October 2021 Volume 12 Article 722528; https://repositorio.uchile.cl/handle/2250/185657Test

الإتاحة: https://doi.org/10.3389/fphys.2021.722528Test
https://repositorio.uchile.cl/handle/2250/185657Test

المؤلفون: Inn-Ray Chu, Rong-Long Pan, Chung-Shi Yang

المصدر: Medicina; Volume 56; Issue 11; Pages: 625

مصطلحات موضوعية: cancer stem cell, differentiation therapy, interleukin-6, glial fibrillary acidic protein, soluble interleukin-6 receptor, tumor necrosis factor-α

الوصف: Background and objectives: Cancer stem cells (CSCs) are obstacles to cancer therapy due to their therapeutic resistance, ability to initiate neoplasia, and roles in tumor relapse and metastasis. Efforts have been made to cure CSCs, such as the use of differentiation therapy, which induces cancer stem-like cells to undergo differentiation and decrease their tumorigenicity. Interleukin 6 (IL-6) upregulates the expression of glial fibrillary acidic protein (GFAP) in C6 glioma cells, indicating that it is able to induce the differentiation of these cells. The C6 glioma cell line forms a high percentage of cancer stem-like cells, leading us to speculate whether IL-6 signaling could modulate the differentiation of tumorigenic C6 glioma cells. However, we observed that IL-6 alone could not efficiently induce the differentiation of these cells. Therefore, different IL-6 signaling elicitors, including IL-6 alone, a combination of IL-6 and soluble IL-6 receptor (IL-6/sIL-6R), and tumor necrosis factor-α (TNF-α) plus IL-6/sIL-6R (TNF-α/IL-6/sIL-6R), were evaluated for their potential use in differentiation therapy. Materials and Methods: The potential of IL-6 signaling elicitors in differentiation therapy were examined by assessing changes in biomarker levels, the rate of cell proliferation, and tumorigenicity, respectively. Results: Enhanced IL-6 signaling could effectively induce C6 glioma cell differentiation, as determined by observed variations in the expression of differentiation, cell cycle, and stem cell biomarkers. Additionally, the total cell population and the tumorigenicity of glioma cells were all considerably reduced after TNF-α/IL-6/sIL-6R treatment. Conclusions: Our findings provide evidence that enhanced IL-6 signaling can efficiently promote tumorigenic C6 glioma cells to undergo differentiation.

وصف الملف: application/pdf

العلاقة: Oncology; https://dx.doi.org/10.3390/medicina56110625Test

الإتاحة: https://doi.org/10.3390/medicina56110625Test

المؤلفون: Foldvari-Nagy, L, Schnabel, T, Dornyei, G, Korcsmaros, T, Lenti, K

المصدر: 7 ; 1

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Cell Biology, IL-6, Cytokine storm, Metalloprotease, Bacteria, COVID-19, SOLUBLE INTERLEUKIN-6 RECEPTOR, STAPHYLOCOCCUS-AUREUS, VIRUS-INFECTION, IL-6 PRODUCTION, ACTIVATION, EXPRESSION, MECHANISM, GENE, TOCILIZUMAB, INDUCTION, Bacterial Proteins, Cytokine Release Syndrome, Humans, Interleukin-6, Metalloproteases, Receptors, SARS-CoV-2, Signal Transduction

الوصف: The cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6Rα. Through this, so-called trans-signaling, IL-6–sIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6Rα, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6Rα shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19.

العلاقة: Cell Communication and Signaling; http://hdl.handle.net/10044/1/94350Test

الإتاحة: https://doi.org/10.1186/s12964-020-00699-3Test
http://hdl.handle.net/10044/1/94350Test

المؤلفون: Mahmud-Al-Rafat, A, Majumder, A, Rahman, KMT, Hasan, AMM, Islam, KMD, Taylor-Robinson, AW, Billah, MM

المصدر: Cytokine , 115 pp. 13-23. (2019)

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Immunology, Virus, Ebola, SARS-CoV, Dengue, Cytokine storm, Antiviral, Pro-inflammatory response, IL-6, ADAM-17, ACUTE-RESPIRATORY-SYNDROME, ALPHA-CONVERTING-ENZYME, NECROSIS-FACTOR-ALPHA, SOLUBLE INTERLEUKIN-6 RECEPTOR, INFLAMMATORY-BOWEL-DISEASE, EBOLA-VIRUS INFECTION, FACTOR-KAPPA-B, DENDRITIC CELLS, TNF-ALPHA, IMMUNE-RESPONSES

الوصف: Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10114104/1/main%20%284%29.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10114104Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10114104/1/main%20%284%29.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10114104Test/