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https://www.readbyqxmd.com/read/28321811/interleukin-2-old-and-new-approaches-to-enhance-immune-therapeutic-efficacy
#1
Pooja Dhupkar, Nancy Gordon
Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28293407/thrombocytopenia-in-patients-with-chronic-hepatitis-c-virus-infection
#2
REVIEW
Sumit Dahal, Smrity Upadhyay, Rashmi Banjade, Prajwal Dhakal, Nabin Khanal, Vijaya Raj Bhatt
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28289419/cytokine-signatures-in-mucocutaneous-and-ocular-beh%C3%A3-et-s-disease
#3
Giuseppe Lopalco, Orso Maria Lucherini, Antonio Lopalco, Vincenzo Venerito, Claudia Fabiani, Bruno Frediani, Mauro Galeazzi, Giovanni Lapadula, Luca Cantarini, Florenzo Iannone
Behçet's disease (BD) is a multi-systemic inflammatory disorder consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis; however, many other organs may be affected. Several pro-inflammatory cytokines, mainly derived from Th1 and Th17 lymphocytes, seem to be involved in different pathogenic pathways leading to development of the clinical manifestations. On this basis, the primary aim of our study was to compare a core set of pro-inflammatory cytokines between patients with BD and healthy control (HC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228280/autocrine-loop-involving-il-6-family-member-lif-lif-receptor-and-stat4-drives-sustained-fibroblast-production-of-inflammatory-mediators
#4
Hung N Nguyen, Erika H Noss, Fumitaka Mizoguchi, Christine Huppertz, Kevin S Wei, Gerald F M Watts, Michael B Brenner
Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordinately upregulated with IL-6 pointed to STAT4 and leukemia inhibitory factor (LIF) as potentially linked. Gene silencing revealed that STAT4 was required for IL-6 transcription. STAT4 was recruited to the IL-6 promoter after fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28186993/therapeutically-blocking-interleukin-11-receptor-%C3%AE-enhances-doxorubicin-cytotoxicity-in-high-grade-type-i-endometrioid-tumours
#5
Amy Winship, Michelle Van Sinderen, Katarzyna Rainczuk, Evdokia Dimitriadis
High grade type I endometrial cancers have poor prognosis. Interleukin (IL)11 is elevated in tumours and uterine lavage with increasing tumour grade in women. IL11 regulates cell cycle, invasion and migration and we recently demonstrated that IL11 receptor (R)α inhibition impaired low and moderate grade endometrial tumourigenesis in vivo. In this report, we hypothesized that micro-RNA(miR)-1 regulates IL11 and that IL11 promotes high grade endometrial tumour growth. We aimed to determine whether combination treatment using an anti-human IL11Rα blocking antibody (Ab) and doxorubicin chemotherapeutic impairs high grade tumour growth...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28161069/interleukin-11-induces-preterm-birth-and-modulates-decidual-inflammasome-gene-expression-in-mice
#6
Amy Winship, Evdokia Dimitriadis
Decidual inflammation and inflammasome activation contribute to the pathogenesis of preterm birth (PTB). Interleukin-(IL)11 exerts complex regulatory effects on inflammation and IL-11 protein is elevated in PTB decidua. We aimed to determine a functional role for IL-11 in parturition or PTB. IL-11 administration during middle-late gestation pregnancy induced preterm birth in 87.5% of mice versus saline controls. Litters from IL-11-treated mothers had reduced offspring weight and numbers of live pups. IL-11 up-regulated decidual gene expression of key components of the inflammasome including IL-1β, Caspase-1 and ASC...
February 2017: Placenta
https://www.readbyqxmd.com/read/28160627/interleukin-11-driven-gastric-tumourigenesis-is-independent-of-trans-signalling
#7
Jesse J Balic, Christoph Garbers, Stefan Rose-John, Liang Yu, Brendan J Jenkins
Deregulated gp130-dependent STAT3 signalling by the pleiotropic cytokine interleukin (IL)-11 has been implicated in the pathogenesis of gastric cancer (GC), the third most common cancer worldwide. While the IL-11-gp130-STAT3 signalling axis has traditionally been thought to exclusively use the membrane-bound IL-11 receptor (mIL-11R), recent evidence suggests that mIL-11R can be proteolytically cleaved to generate a soluble form (sIL-11R) which can elicit trans-signalling. Since the role of IL-11 trans-signalling in disease pathogenesis is unknown, here we have employed the IL-11-driven gp130(F/F) spontaneous model of GC to determine whether IL-11 trans-signalling promotes gastric tumourigenesis...
February 1, 2017: Cytokine
https://www.readbyqxmd.com/read/28116426/-effects-and-mechanisms-of-egr-1-on-inflammatory-responses-induced-by-mechanical-stress-in-human-periodontal-ligament-cells
#8
Hai-Yan Hu, Zhi-Biao Gao
PURPOSE: To investigate the effects and mechanisms of silencing Egr-1 on MS-mediated secretion and expression of inflammatory cytokines in hPDLs. METHODS: The secretion and expression of IL-1β, IL-6, IL-8 and IL-11 were detected using ELISA and RT-PCR when cells were cultured with or without various duration (6, 12, 24 and 48 h) and force (3%, 6%, 12%, 15%) of mechanica stress (MS). RT-PCR and Western blotting were used to evaluate the expression of Egr-1 under a 12% MS for 24 h...
October 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28061947/b-lymphocytes-forming-follicle-like-structures-in-the-lung-tissue-of-tuberculosis-infected-mice-dynamics-phenotypes-and-functional-activity
#9
Irina Linge, Alexander Dyatlov, Elena Kondratieva, Vadim Avdienko, Alexander Apt, Tatiana Kondratieva
During tuberculosis (TB) infection, B cells form follicles in close vicinity of lung granuloma. We assessed the dynamics of follicle formation, surface phenotypes and functional activity of lung B cells during TB course in genetically susceptible mice. The follicles appeared early post infection and peaked at weeks 7-8. Lung B cells resembled classical B2 cells (CD19(+)IgMloIgD(hi)CD1d(-)CD21/35(int)CD5(-)CD11b(-)CD43(-)), but differed from them by the absence of B2 marker CD23. Lung B-cells constitutively expressed MHC II molecules, presented mycobacterial antigens to immune CD4(+) T-cells and produced high amounts of IL-6 and IL-11, but no classical type 1 (TNF-α, IFN-γ), or anti-inflammatory (IL-10, TGF-β) cytokines...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/27998870/-expressions-of-inflammatory-cytokines-in-intestinal-mucosa-and-their-prognostic-value-in-patients-with-ulcerative-colitis
#10
An-Na Lin, Yu-Qing Li, Mu-Xiao Zhong, Jiang Liu, Qian Dai, Wei Zhu, Ya-Li Zhang
OBJECTIVE: To detect the expressions of IL-17, IL-23, IL-22 and IL-11 in the intestinal mucosa of patients with ulcerative colitis (UC) and analyze their prognostic values. METHODS: Forty patients with active UC, 15 with UC in remission and 15 healthy subjects were examined for the expressions and distribution of IL-17, IL-23, IL-22, and IL-11 in the colorectal mucosausing immunohistochemistry. We further collected the data from 40 patients with routine therapy and regular follow-up and compared the expressions of those cytokines according to the condition of mucosal healing...
December 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27922075/cancer-associated-fibroblasts-treated-with-cisplatin-facilitates-chemoresistance-of-lung-adenocarcinoma-through-il-11-il-11r-stat3-signaling-pathway
#11
Leilei Tao, Guichun Huang, Rui Wang, Yan Pan, Zhenyue He, Xiaoyuan Chu, Haizhu Song, Longbang Chen
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916836/expression-purification-and-characterization-of-interleukin-11-orthologues
#12
Andrei S Sokolov, Alexei S Kazakov, Valery V Solovyev, Ramis G Ismailov, Vladimir N Uversky, Yulia S Lapteva, Roman V Mikhailov, Ekaterina V Pavlova, Iana O Terletskaya, Ludmila V Ermolina, Sergei E Permyakov, Eugene A Permyakov
Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11...
November 29, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27901021/tmed3-promotes-hepatocellular-carcinoma-progression-via-il-11-stat3-signaling
#13
Hao Zheng, Yuan Yang, Jun Han, Wei-Hua Jiang, Cheng Chen, Meng-Chao Wang, Rong Gao, Shuai Li, Tao Tian, Jian Wang, Li-Jun Ma, Hao Ren, Wei-Ping Zhou
Transmembrane p24 trafficking protein 3(TMED3) is a metastatic suppressor in colon cancer, but its function in the progression of hepatocellular carcinoma (HCC) is unknown. Here, we report that TMED3 was up-regulated in HCC and portal vein tumor thrombus. TMED3 up-regulation in HCC was significantly correlated with aggressive characteristics and predicted poor prognosis in HCC patients. TMED3 overexpression in HCC cell lines promoted cell migration and invasion. In contrast, TMED3 knockdown suppressed HCC metastasis both in vitro and in vivo...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885183/-osteoporosis-and-mechano-biosciences
#14
Toshio Matsumoto
Mechanical unloading due to long-term bedrest or microgravity during spaceflight causes a devastating influence on bone. Although bisphosphonates can prevent bone loss and hypercalciuria by mechanical unloading for up to 6 months, the influence of unloading for longer period of time is unknown. This is because mechanical loading is one of the most important stimuli for bone formation. Mechanical stress activates several intracellular signaling pathways. Among them, activation of stress-activated cation channel by fluid shear stress stimulates ERK-CREB signaling to enhance the expression of fos family transcription factors, which stimulates IL-11 expression in osteoblastic cells...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27884519/production-and-characterization-of-genetically-modified-human-il-11-variants
#15
Emiko Sano, Toshiaki Takei, Takuya Ueda, Kouhei Tsumoto
Interleukin-11 (IL-11) has been expected as a drug on severe thrombocytopenia caused by myelo-suppressive chemotherapy. Whereas, development of IL-11 inhibitor is also expected for a treatment against IL-11 related cancer progression. Here, we will demonstrate the creation of various kinds of genetically modified hIL-11s. Modified vectors were constructed by introducing N- or O-glycosylation site on the region of hIL-11 that does not belong to the core α-helical motif based on the predicted secondary structure...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27878687/aptamers-against-pro-and-anti-inflammatory-cytokines-a-review
#16
REVIEW
Maryam Boshtam, Seddigheh Asgary, Shirin Kouhpayeh, Laleh Shariati, Hossein Khanahmad
Inflammatory disorders result from continuous inflammation in injured sites. Many molecules are involved in this process; the inhibition of which could prevent the inflammation. Chemokines are a group of these biological mediators which are categorized into pro-, anti-, and pro-/anti-inflammatory. Thus, targeting these essential molecules can be an effective way for prevention and control of inflammatory diseases. Various therapeutic agents have been developed for primary and secondary prevention of these disorders, but each of them has its own limitations...
November 23, 2016: Inflammation
https://www.readbyqxmd.com/read/27872193/critical-contribution-of-nuclear-factor-erythroid-2-related-factor-2-nrf2-to-electrophile-induced-interleukin-11-production
#17
Takashi Nishina, Yutaka Deguchi, Ryosuke Miura, Soh Yamazaki, Yasuhiro Shinkai, Yuko Kojima, Ko Okumura, Yoshito Kumagai, Hiroyasu Nakano
Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays a crucial role in protection of cells from electrophile-induced toxicity through up-regulating phase II detoxifying enzymes and phase III transporters. We previously reported that oxidative stress induces up-regulation of interleukin-11 (IL-11), a member of the IL-6 family that ameliorates acetaminophen-induced liver toxicity. However, a role for IL-11 in protection of cells from electrophile-induced toxicity remains unclear...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27784384/-thrombocytopoietic-efficacy-of-pegylated-recombinant-human-interleukin-11-mutein-in-myelosuppressed-mice
#18
Shan-Shan Ma, Seong-Hyun Ho, Hong-Ling Wang, Li-Ya Nie, Song-Shan Xu
OBJECTIVE: To evaluate the effect of PEGylated IL-11 mutein (PEG-mIL 11) with different dose or injection frequency on thrombocytopenia in myelosuppressed mice and to compare its effect with mIL-11, so as to provide reference data for clinical use. METHODS: Myelosuppressive model with thrombocyopenia was produced in BALB/c mice by whole body (60)Co γ-ray irradiation in dose of administration 2.5 Gy followed by i.p. injections of carboplatin at 50 mg/kg. In study of injection frequency, 30 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1, 4, 7), mIL-11 group [200 µg/(kg·d)×9 d], PEG-mIL 11 A group [111800 µg/(kg·d)×1 d (d 1)], PEG-mIL 11 B group 900 µg/(kg·d)×2 d (d 1,5), and PEG-mIL 11 C group [600 µg/(kg·d)×3 d (d 1,4,7)]...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27750106/breast-cancer-osteomimicry-and-its-role-in-bone-specific-metastasis-an%C3%A2-integrative-systematic-review-of-preclinical-evidence
#19
REVIEW
Olugbenga Awolaran, Susan A Brooks, Verna Lavender
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016...
December 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27746864/repairing-effects-of-interleukin-11-il-11-towards-high-dose-methotrexate-induced-rat-small-intestinal-mucositis-and-its-impacts-on-t-lymphoblastic-leukemia-cell-line
#20
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
August 2016: Iranian Journal of Basic Medical Sciences
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