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Interleukine 2

Longcan Mei, Yanping Zhou, Lizhe Zhu, Changlin Liu, Zhuo Wu, Fangkui Wang, Gefei Hao, Di Yu, Hong Yuan, Yanfang Cui
A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm...
March 20, 2018: International Journal of Molecular Sciences
Iwona Krela-Kaźmierczak, Aleksandra Szymczak-Tomczak, Liliana Łykowska-Szuber, Ewa Wysocka, Michał Michalak, Kamila Stawczyk-Eder, Katarzyna Waszak, Krzysztof Linke, Piotr Eder
BACKGROUND: Cytokines are mediators of inflammatory processes in the course of inflammatory bowel disease (IBD) and participate in the bone metabolism. Interleukin 6 (IL-6) initiates osteoclastogenesis by modulating the activity of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin. OBJECTIVES: The aim of the study was to evaluate bone mineral density (BMD) by densitometry and the concentration of interleukin 6, osteoprotegerin (OPG) and sRANKL protein (sRANKL) by ELISA in patients with IBD in relation to the control group; to assess the relationship between IL-6, OPG, sRANKL and BMD; and to assess the impact of disease duration and number hospitalization on BMD...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Jessica A Walsh, Oluwakayode Adejoro, Benjamin Chastek, Jacqueline B Palmer, Peter Hur
BACKGROUND: In patients with psoriatic arthritis (PsA), limited data exist regarding patterns of biologic therapy use. OBJECTIVE: To examine treatment patterns and therapy modifications in U.S. patients with PsA receiving a tumor necrosis factor inhibitor (TNFi) or an anti-interleukin (IL)-12/23 inhibitor. METHODS: Adults with PsA who newly initiated a biologic therapy (index biologic) between January 1, 2013, and January 31, 2015, were included from the Optum Research Database...
March 20, 2018: Journal of Managed Care & Specialty Pharmacy
Sufian S Ahmad, Michael T Hirschmann, Roland Becker, Ahmed Shaker, Atesch Ateschrang, Marius J B Keel, Christoph E Albers, Lukas Buetikofer, Sithombo Maqungo, Ulrich Stöckle, Sandro Kohl
PURPOSE: (1) To determine the overall accuracy of synovial alpha-defensin, synovial C-reactive protein (sCRP), interleukin-6 (sIL-6), and leukocyte esterase (sLE) as diagnostic markers for periprosthetic joint infection (PJI) and (2) to independantly evaluate the accuracy of both the laboratory-based ELISA alpha-defensin test and the Synovasure™ alpha-defensin test kit. METHODS: An EMBASE and MEDLINE (PubMed) database search was performed using a set of professionally set search terms...
March 20, 2018: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
Cem Gabay, Jérôme Msihid, Moshe Zilberstein, Caroline Paccard, Yong Lin, Neil M H Graham, Anita Boyapati
Introduction: Interleukin-6 (IL-6) orchestrates formation of an inflammatory pannus, leading to joint damage in rheumatoid arthritis (RA). Sarilumab is a human monoclonal antibody blocking the IL-6Rα. In TARGET (NCT01709578), a phase 3 study in adults with moderate-to-severe RA and inadequate response or intolerance to tumour necrosis factor inhibitors, subcutaneous sarilumab 200 mg or 150 mg every 2 weeks (q2w) plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) significantly reduced disease activity versus placebo plus csDMARDs...
2018: RMD Open
Hui Cao, Senlin Li, Rui Xie, Na Xu, Ying Qian, Hongdan Chen, Qinyu Hu, Yihong Quan, Zhihong Yu, Junjun Liu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB)...
2018: Frontiers in Pharmacology
Hanna D Bremer, Nils Landegren, Ronald Sjöberg, Åsa Hallgren, Stefanie Renneker, Erik Lattwein, Dag Leonard, Maija-Leena Eloranta, Lars Rönnblom, Gunnel Nordmark, Peter Nilsson, Göran Andersson, Inger Lilliehöök, Kerstin Lindblad-Toh, Olle Kämpe, Helene Hansson-Hamlin
Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs...
March 19, 2018: Scientific Reports
Emma L Kuan, Steven F Ziegler
Tumors actively manipulate the immune response through the production of factors that attract immune cells and subsequently alter their ability to recognize and effectively remove the tumor. While this mechanism for evading the immune system is an important aspect of tumor survival, the factors that serve as primary growth factors for the tumor are less understood. Here we demonstrate a previously unknown mechanism by which breast-cancer cells manipulate tumor-infiltrating myeloid cells to maintain their survival...
March 19, 2018: Nature Immunology
Corinne Cayrol, Anais Duval, Pauline Schmitt, Stephane Roga, Mylène Camus, Alexandre Stella, Odile Burlet-Schiltz, Anne Gonzalez-de-Peredo, Jean-Philippe Girard
Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL ), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor that detected proteolytic activities associated with various environmental allergens across four kingdoms, including fungi, house dust mites, bacteria and pollens. When exposed to allergen proteases, IL-33FL was rapidly cleaved in its central 'sensor' domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells...
March 19, 2018: Nature Immunology
Eugenia Roupakia, Georgios Markopoulos, Evangelos Kolettas
Liu and colleagues investigated the expression of matrix matalloproteinases (MMPs) in human periodontal ligament fibroblasts (hPDLFs) regulated by interleukin-12 (IL-12), a cytokine implicated in inflammatory and immune responses. They showed that IL-12 activates canonical NF-kappaB signalling leading to increased expression of MMP-1 (Interstitial collagenase), MMP-3 (stromelysin 1) and MMP-13 (collagenase 3), and to a smaller reduction in the expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) at both mRNA and protein levels, with corresponding changes in the secreted levels of these extracellular matrix-remodelling and immune regulatory metalloproteinases...
March 19, 2018: Bioscience Reports
Xinyan Wang, Linyong Du, He Wei, Anying Zhang, Kun Yang, Hong Zhou
Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT family in response to cytokines and growth factors. In mammals, alternative splicing of STAT3 generates STAT3α and STAT3β, which have distinct and overlapping functions. In the previous study, we have identified two spliceforms of Stat3α (Stat3α1 and Stat3α2) possessing all functional domains of Stat3 in grass carp (Ctenopharyngodon idella). In the present study, two Stat3β variants (Stat3β1 and Stat3β2) without C-terminal transactivation domain were isolated from this species, and their transcripts were ubiquitously expressed in all examined tissues with the highest levels in liver...
March 16, 2018: Fish & Shellfish Immunology
Yuhong Li, Qi Ren, Lingyan Zhu, Yingshu Li, Jinfeng Li, Yiyang Zhang, Guoying Zheng, Tiesheng Han, Shufeng Sun, Fumin Feng
BACKGROUND: This investigation aimed to evaluate the role of methylation in the regulation of microRNA (miR)-122, miR-125b and miR-106b gene expression and the expression of their target genes during isoniazid (INH)-induced liver injury. METHODS: Rats were given INH 50 mg kg- 1 ·d- 1 once per day for 3, 7, 10, 14, 21 and 28 days and were sacrificed. Samples of blood and liver were obtained. RESULTS: We analysed the methylation and expression levels of miR-122, miR-125b and miR-106b and their potential gene targets in livers...
March 20, 2018: BMC Pharmacology & Toxicology
Mariana Castro Martins, Mandy J Peffers, Katie Lee, Luis M Rubio-Martinez
BACKGROUND: Intra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA. However, there is limited evidence on the anti-inflammatory and modulatory properties of stanozolol on articular tissues. The objective of the current study was to evaluate the effects of stanozolol on chondrocyte viability and gene expression in normal equine chondrocytes and an inflammatory in vitro system of OA (interleukin-1β (IL-1β) treated chondrocytes)...
March 20, 2018: BMC Veterinary Research
Shu-Long Li, Yun Yu, Peng Yang, Hui Wang, Cheng Zhang, Min Liu, Jia-Xiang Zhang, Tong Shen, Changhao Wu, Qi-Xing Zhu
The role of environmental factors in autoimmune diseases has been increasingly recognized. While major advance has been made in understanding biological pathogen-induced autoimmune diseases, chemically triggered autoimmunity is poorly understood. Trichloroethylene (TCE), a common environmental pollutant, has recently been shown to induce autoimmunity. This study explored whether TCE could cause imbalance of T helper (Th) cell subsets which would contribute to the pathogenesis of TCE-induced medicamentosa-like dermatitis...
January 1, 2018: International Journal of Toxicology
Jill Koshiol, Yu-Tang Gao, Amanda Corbel, Troy J Kemp, Ming-Chang Shen, Allan Hildesheim, Ann W Hsing, Asif Rashid, Bingsheng Wang, Ruth M Pfeiffer, Ligia A Pinto
BACKGROUND: Inflammatory proteins could help identify individuals most likely to have gallbladder cancer (GBC) among those waiting for cholecystectomy. METHODS: We analyzed 49 circulating inflammation-related proteins in 144 patients with GBC and 150 patients with gallstones. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs for protein quantiles and GBC versus gallstones. Using proteins associated with early GBC (stage 1-2) that were selected in stepwise logistic regression, we created an inflammation score and explored the potential utility for risk stratification...
March 16, 2018: Cancer Epidemiology
Hui Gao, Zhuo Dong, Xinkou Gong, Juancong Dong, Yuyu Zhang, Wei Wei, Rui Wang, Shunzi Jin
Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype-related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation's immune effects and their relationship with Th1/Th2 immunity...
March 15, 2018: Journal of Radiation Research
Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan
The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis...
March 19, 2018: PLoS Pathogens
David P Perrault, Athanasios Bramos, Xingtian Xu, Songtao Shi, Alex K Wong
Impaired healing of the skin is a notable cause of patient morbidity and mortality. In diabetic individuals, dysregulated inflammation contributes to delayed wound healing. Specific immunomodulatory agents may have a role in the treatment of diabetic wounds. One of these molecules is interleukin-1 receptor antagonist (Anakinra; Amgen Corp.). Although interleukin-1 receptor antagonist (Anakinra; Amgen Corp.) is approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease, little is known about the local use this drug in cutaneous wound healing...
March 16, 2018: Annals of Plastic Surgery
Mahmood Ahmad Khan, Mohd Jahir Khan
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, affecting almost 1% of world population. Although the exact cause of RA is not known but the complex interaction between inflammatory mediators like tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) is accountable for cartilage destruction in joints. Gold is used for arthritis treatment since long without knowing its mechanism of action. Hence, the present study was designed to assess antiarthritic activity of nanogold (AuNGs) in collagen-induced arthritic (CIA) rat model by virtue of decreasing inflammatory mediators and oxidative stress...
March 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Wen Tan, Lin Chen, Ya-Xin Wang, Li-Sha Hu, Wei Xiong, You Shang, Shang-Long Yao
Background: Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS). Methods: BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng)...
March 19, 2018: Chinese Medical Journal
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