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https://www.readbyqxmd.com/read/29446854/overexpression-of-il-35-in-intrahepatic-cholangiocarcinoma-isa-prognostic-indicator-after-curative-resection
#1
Meixia Zhang, Wei Gan, Chuyu Jing, Susu Zheng, Juan Zhang, Hujia Shen, Xin Xu, Jiajia Lin, Boheng Zhang, Shuangjian Qiu
Interleukin-35 (IL-35) is implicated in tumorigenesis, but the exact impact on intrahepatic cholangiocarcinoma (ICC) is not clearly. The aim of present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry (IHC) was applied to explore IL-35 expression as well as IL-35R in 102 ICC patients. The results showed IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis, TNM stage and vascular invasion and was independent prognostic factor for patients' OS and RFS...
February 15, 2018: Cancer Science
https://www.readbyqxmd.com/read/29436471/drug-induced-modulation-of-gp130-signalling-prevents-articular-cartilage-degeneration-and-promotes-repair
#2
Ruzanna Shkhyan, Ben Van Handel, Jacob Bogdanov, Siyoung Lee, Yifan Yu, Mila Scheinberg, Nicholas W Banks, Sean Limfat, Arthur Chernostrik, Carlos Eduardo Franciozi, Mohammad Parvez Alam, Varghese John, Ling Wu, Gabriel B Ferguson, Ali Nsair, Frank A Petrigliano, C Thomas Vangsness, Kanagasabai Vadivel, Paul Bajaj, Liming Wang, Nancy Q Liu, Denis Evseenko
OBJECTIVE: Human adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs...
February 7, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29417587/hyperactive-gp130-stat3-driven-gastric-tumourigenesis-promotes-submucosal-tertiary-lymphoid-structure-development
#3
David G Hill, Liang Yu, Hugh Gao, Jesse J Balic, Alison West, Hiroko Oshima, Louise McLeod, Masanobu Oshima, Awen Gallimore, Kimberley D'Costa, Prithi S Bhathal, William Sievert, Richard L Ferrero, Brendan J Jenkins, Gareth W Jones
Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation-associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour-associated TLSs remain ill-defined. Here, we observed tumour-associated TLSs in a preclinical mouse model (gp130F/F ) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL-6 family signalling receptor, gp130...
February 8, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29410184/interleukin-6-potentiates-fc%C3%AE%C2%B5ri-induced-pgd2-biosynthesis-and-induces-vegf-from-human-in-situ-matured-skin-mast-cells
#4
Cody McHale, Zahraa Mohammed, Juline Deppen, Gregorio Gomez
BACKGROUND: Interleukin-6 is a gp130 utilizing cytokine that is consistently associated with allergic diseases like asthma and urticaria in humans where mast cells are known to play a critical role. However, the role of IL-6 in allergic disease in not known. IL-6 was reported to enhance degranulation of in vitro-derived mast cells, but the effect of IL-6 on mediator release from human in situ-matured tissue-isolated mast cells had not been reported. METHODS: Human mature mast cells were isolated and purified from normal skin tissue from different donors...
February 1, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29408481/mir-7-5p-functions-as-a-tumor-suppressor-by-targeting-sox18-in-pancreatic-ductal-adenocarcinoma
#5
Weihua Zhu, Yazhou Wang, Dafang Zhang, Xin Yu, Xisheng Leng
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Recently, many kinds of microRNAs (miRNAs) have been found to play a significant role in development of PDAC. However, there is no investigation about expression and function of miR-7-5p in PDAC. In this study, we found that miR-7-5p was down-regulated in PDAC tissues and its low expression level indicated a poor survival rate for PDAC patients. By bioinformatic analysis, we found that miR-7-5p targeted SOX18, and there was a negative correlation between them in PDAC tissues...
February 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29403488/absence-of-tumor-necrosis-factor-supports-alternative-activation-of-macrophages-in-the-liver-after-infection-with-leishmania-major
#6
Shanshan Hu, Cameron Marshall, Jocelyn Darby, Wei Wei, Alan Bruce Lyons, Heinrich Körner
The absence of tumor necrosis factor (TNF) causes lethal infection by Leishmania major in normally resistant C57BL/6J (B6.WT) mice. The underlying pathogenic mechanism of this fatal disease has so far remained elusive. We found that B6.WT mice deficient for the tnf gene (B6.TNF-/-) displayed not only a non-healing cutaneous lesion but also a serious infection of the liver upon L. major inoculation. Infected B6.TNF-/- mice developed an enlarged liver that showed increased inflammation. Furthermore, we detected an accumulating monocyte-derived macrophage population (CD45+F4/80+CD11bhiLy6Clow) that displayed a M2 macrophage phenotype with high expression of CD206, arginase-1, and IL-6, supporting the notion that IL-6 could be involved in M2 differentiation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29389248/the-role-of-gp130-in-basal-and-exercise-trained-skeletal-muscle-mitochondrial-quality-control
#7
Dennis K Fix, Justin P Hardee, Song Gao, Brandon N VanderVeen, Kandy T Velazquez, James A Carson
The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein 130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscle's metabolic response to exercise, gp130's role in mitochondrial quality control involving fission, fusion, mitophagy and biogenesis is not well understood. Therefore, we examined gp130's role in basal and exercise-trained muscle mitochondrial quality control...
February 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29363180/separate-roles-of-il-6-and-oncostatin-m-in-mouse-macrophage-polarization-in-vitro-and-in-vivo
#8
Anisha Dubey, Laura Izakelian, Ehab A Ayaub, Lilian Ho, Kyle Stephenson, Steven Wong, Karen Kwofie, Richard C Austin, Fernando Botelho, Kjetil Ask, Carl D Richards
Arginase-1 (Arg-1)-expressing M2-like macrophages are associated with Th2-skewed immune responses, allergic airway pathology, ectopic B16 melanoma cancer growth in murine models, and can be induced by Oncostatin M (OSM) transient overexpression in vivo. Here, we compare OSM to the gp130-cytokine IL-6 in mediating macrophage polarization, and find that IL-6 overexpression alone (Ad vector, AdIL-6) did not induce Arg-1 protein in mouse lungs at day 7, nor ectopic melanoma tumor growth at day 14, in contrast to overexpression of OSM (AdOSM)...
November 27, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29360942/il-6-trans-activation-contributes-to-aldosterone-induced-cardiac-fibrosis
#9
Chia-Hung Chou, Chi-Sheng Hung, Che-Wei Liao, Lin-Hung Wei, Ching-Way Chen, Chia-Tung Shun, Wen-Fen Wen, Cho-Hua Wan, Xue-Ming Wu, Yi-Yao Chang, Vin-Cent Wu, Kwan-Dun Wu, Yen-Hung Lin
Aims: An excess of aldosterone results in cardiac remodeling and fibrosis. Interleukin-6 (IL-6) is a key mediator in the fibrotic process, however the effect of aldosterone on the expression of IL-6 remains unclear. We investigated whether aldosterone induces the expression of IL-6 and thereby contributes to the fibrotic process. Methods and Results: In this clinical study, we prospectively enrolled 25 patients with primary aldosteronism (PA) and 26 patients with essential hypertension (EH)...
January 19, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29322414/dissecting-interleukin-6-classic-and-trans-signaling-in-inflammation-and-cancer
#10
Christoph Garbers, Stefan Rose-John
Interleukin-6 is a cytokine synthesized by many cells in the human body. IL-6 binds to a membrane bound IL-6R, which is only present on hepatocytes, some epithelial cells and some leukocytes. The complex of IL-6 and IL-6R binds to the ubiquitously expressed receptor subunit gp130, which forms a homodimer and thereby initiates intracellular signaling via the JAK/STAT and the MAPK pathways. IL-6R expressing cells can cleave the receptor protein to generate a soluble IL-6R (sIL-6R), which can still bind IL-6 and can associate with gp130 and induce signaling even on cells, which do not express IL-6R...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29276788/a-role-for-soluble-il-6-receptor-in-osteoarthritis
#11
Graham Akeson, Charles J Malemud
Interleukin-6 (IL-6) is one of several pro-inflammatory cytokines present at elevated levels in the synovial fluid of individuals with confirmed clinical diagnosis of rheumatoid arthritis (RA) and osteoarthritis (OA). The mechanism of action of IL-6 was shown to involve its capacity to interact with a membrane-bound IL-6 receptor (mIL-6Rα), also known as the "classical" IL-6 pathway, or through its interaction with a soluble IL-6 receptor (sIL-6R) termed the "trans-signaling" pathway. Activation of downstream signaling is transduced via these IL-6 receptors and principally involves the Janus Kinase/Signal Transduction and Activators of Transcription (JAK/STAT) signaling pathway that is further regulated by glycoprotein-130 (gp130) interacting with the IL-6/mIL-6R complex...
2017: Journal of Functional Morphology and Kinesiology
https://www.readbyqxmd.com/read/29247146/synoviocytes-derived-interleukin-35-potentiates-b-cell-response-in-patients-with-osteoarthritis-and-rheumatoid-arthritis
#12
Ngar-Woon Kam, Dehua Liu, Zhe Cai, Wah-Yan Mak, Chun-Kwok Wong, Kwok-Hing Chiu, Kam-Yiu Wong, Wai-Leuk Tsang, Lai-Shan Tam
OBJECTIVE: Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA). METHODS: IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. IL-35 receptor (IL-35R) expression on B cells dissociated from synovium and periphery of patients with RA, OA, and healthy donor controls (HC) was determined by flow cytometry...
December 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/29245982/endothelial-derived-interleukin-6-induces-cancer-stem-cell-motility-by-generating-a-chemotactic-gradient-towards-blood-vessels
#13
Hong Sun Kim, Yu-Chih Chen, Felipe Nör, Kristy A Warner, April Andrews, Vivian P Wagner, Zhaocheng Zhang, Zhixiong Zhang, Manoela D Martins, Alexander T Pearson, Euisik Yoon, Jacques E Nör
Recent evidence suggests that the metastatic spread of head and neck squamous cell carcinomas (HNSCC) requires the function of cancer stem cells endowed with multipotency, self-renewal, and high tumorigenic potential. We demonstrated that cancer stem cells reside in perivascular niches and are characterized by high aldehyde dehydrogenase (ALDH) activity and high CD44 expression (ALDHhighCD44high) in HNSCC. Here, we hypothesize that endothelial cell-secreted interleukin-6 (IL-6) contributes to tumor progression by enhancing the migratory phenotype and survival of cancer stem cells...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29237553/the-snp-rs4252548-r112h-which-is-associated-with-reduced-human-height-compromises-the-stability-of-il-11
#14
Juliane Lokau, Sascha Göttert, Philipp Arnold, Stefan Düsterhöft, David Massa López, Joachim Grötzinger, Christoph Garbers
Height is a complex human phenotype that is influenced by variations in a high number of genes. Recently, a single nucleotide polymorphism (SNP) within IL11 (rs4252548) has been described to be associated with height in adults of European ancestry. This coding SNP leads to the exchange of Arg-112 to His-112 within the cytokine Interleukin-11 (IL-11), which has a well-established role in osteoclast development and bone turnover. The functional consequences of the R112H mutation are unknown so far. In this study, we show by molecular replacement that Arg-112 does not participate in binding of IL-11 to its receptors IL-11R and glycoprotein 130 (gp130)...
December 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29235178/the-gp130-cytokine-il-11-regulates-engraftment-of-vav1-hematopoietic-stem-and-progenitor-cells-in-lethally-irradiated-recipients
#15
Serena De Vita, Yanhua Li, Chad E Harris, Meaghan K McGuinness, Clement Ma, David A Williams
During bone marrow transplantation (BMT), hematopoietic stem and progenitor cells (HSPCs) respond to signals from the hematopoietic microenvironment (HM) by coordinately activating molecular pathways through Rho GTPases, including Rac. We have previously shown that deletion of Vav1, a hematopoietic-specific activator of Rac, compromises engraftment of transplanted adult HSPCs without affecting steady-state hematopoiesis in adult animals. Here, we show that Vav1-/- fetal HSPCs can appropriately seed hematopoietic tissues during ontogeny but cannot engraft into lethally irradiated recipients...
December 13, 2017: Stem Cells
https://www.readbyqxmd.com/read/29227830/cell-surface-markers-for-the-identification-and-study-of-human-naive-pluripotent-stem-cells
#16
REVIEW
Oliver Trusler, Ziyi Huang, Jacob Goodwin, Andrew L Laslett
Characterisation of mouse pluripotent stem cells has revealed two distinct pluripotent states, naive and primed, that maintain characteristics of the pre and post implanted epiblast respectively. Recent studies have developed several culture systems that seek to recapitulate the naive phenomenon in human pluripotent stem cells. Therefore, robust methods to isolate these cells will be fundamental to assess their potential in modelling human development and disease. Here we review current methods for human naive pluripotent culture and collate a list of cell surface antigens that have been identified as markers to differentiate naive from primed human pluripotent stem cells...
December 2, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29207075/blocking-interleukin-6-signaling-inhibits-cell-viability-proliferation-glycolysis-and-colony-forming-activity-of-human-medulloblastoma-cells
#17
Xiang Chen, Jia Wei, Chenglong Li, Christopher R Pierson, Jonathan L Finlay, Jiayuh Lin
Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL‑6) have tumor-promoting activity and are associated with poor survival outcomes in many cancers. Additionally, the IL‑6/GP130/STAT3 axis has been widely studied due to its pivotal role in tumor development and maintenance in a number of tissue types, including the cerebellum. However, the connection between IL‑6 signaling and medulloblastoma progression is largely unexplored. In the present study, we observed that IL‑6 induced medulloblastoma cell viability, cell proliferation and glycolysis...
November 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29195127/rapamycin-synergizes-with-cisplatin-in-antiendometrial-cancer-activation-by-improving-il-27-stimulated-cytotoxicity-of-nk-cells
#18
Wen-Jie Zhou, Kai-Kai Chang, Ke Wu, Hui-Li Yang, Jie Mei, Feng Xie, Da-Jin Li, Ming-Qing Li
Natural killer (NK) cell function is critical for controlling initial tumor growth and determining chemosensitivity of the tumor. A synergistic relationship between rapamycin and cisplatin in uterine endometrial cancer (UEC) in vitro has been reported, but the mechanism and the combined therapeutic strategy for endometrial cancer (EC) are still unknown. We found a positive correlation between the level of IL-27 and the differentiated stage of UEC. The increase of IL-27 in uterine endometrial cancer cell (UECC) lines (Ishikawa, RL95-2 and KLE) led to a high cytotoxic activity of NK cells to UECC in the co-culture system...
November 28, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29191994/correction-for-cousins-and-nicholas-role-of-human-herpesvirus-8-interleukin-6-activated-gp130-signal-transducer-in-primary-effusion-lymphoma-cell-growth-and-viability
#19
Emily Cousins, John Nicholas
No abstract text is available yet for this article.
December 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29186034/cellular-and-oxidative-mechanisms-associated-with-interleukin-6-signaling-in-the-vasculature
#20
REVIEW
Sean P Didion
Reactive oxygen species, particularly superoxide, promote endothelial dysfunction and alterations in vascular structure. It is increasingly recognized that inflammatory cytokines, such as interleukin-6 (IL-6), contribute to endothelial dysfunction and vascular hypertrophy and fibrosis. IL-6 is increased in a number of cardiovascular diseases, including hypertension. IL-6 is also associated with a higher incidence of future cardiovascular events and all-cause mortality. Both immune and vascular cells produce IL-6 in response to a number of stimuli, such as angiotensin II...
November 29, 2017: International Journal of Molecular Sciences
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