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IL-22 binding protein

Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
Jian Yang, Zhixing Fan, Jun Yang, Jiawang Ding, Chaojun Yang, Lihua Chen
Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR-22 may protect against myocardial I/R injury via anti-apoptosis in rats by targeting cAMP response element-binding protein binding protein (CBP). However, the specific function of miR-22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury...
November 2016: Experimental and Therapeutic Medicine
Dana Ditgen, Emmanuela M Anandarajah, Jan Hansmann, Dominic Winter, Guido Schramm, Klaus D Erttmann, Eva Liebau, Norbert W Brattig
The cellular redox state is important for the regulation of multiple functions and is essential for the maintenance of cellular homeostasis and antioxidant defense. In the excretory/secretory (E/S) products of Strongyloides ratti and Trichuris suis sequences for thioredoxin (Trx) and Trx-like protein (Trx-lp) were identified. To characterize the antioxidant Trx-lp and its interaction with the parasite's mucosal habitat, S. ratti and T. suis Trx-lps were cloned and recombinantly expressed. The primary antioxidative activity was assured by reduction of insulin and IgM...
2016: Journal of Parasitology Research
Penelope Pelczar, Mario Witkowski, Laura Garcia Perez, Jan Kempski, Anna G Hammel, Leonie Brockmann, Dörte Kleinschmidt, Sandra Wende, Cathleen Haueis, Tanja Bedke, Marco Witkowski, Susanne Krasemann, Stefan Steurer, Carmen J Booth, Philipp Busch, Alexandra König, Ursula Rauch, Daniel Benten, Jakob R Izbicki, Thomas Rösch, Ansgar W Lohse, Till Strowig, Nicola Gagliani, Richard A Flavell, Samuel Huber
Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic inflammation remain unclear. Here we report that CD4(+) T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell-derived IL-22BP. Lastly, intestinal CD4(+) T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor-α (anti-TNF-α), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22...
October 21, 2016: Science
Mulalibieke Heizhati, Nanfang Li, Liang Shao, Xiaoguang Yao, Yingchun Wang, Jing Hong, Ling Zhou, Delian Zhang, Guijuan Chang, Suofeiya Abulikemu
PURPOSE: Sleep architecture can be affected by alteration in circulating lipopolysaccaride and cytokines. However, still unknown are the effects of lipopolysaccaride-binding protein (LBP) on sleep architecture. Therefore, potential relationship between alteration in serum LBP concentrations and sleep architecture was analyzed. METHODS: This is a cross-sectional study. Consecutive 54 hypertensive males, aged 30-65 years. and with no obstructive sleep apnea via polysomnography, were recruited...
October 13, 2016: Sleep & Breathing, Schlaf & Atmung
Chrissie Lim, MeeAe Hong, Ram Savan
The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue homeostasis and immunosurveillance. Dysregulation of IL-22 signaling causes inflammatory diseases. IL-22 binding protein (IL-22BP; encoded by IL22RA2) is a soluble IL-22 receptor, which antagonizes IL-22 activity and has genetic associations with autoimmune diseases...
2016: Science Signaling
Steven G Coca, Girish N Nadkarni, Amit X Garg, Jay Koyner, Heather Thiessen-Philbrook, Eric McArthur, Michael G Shlipak, Chirag R Parikh
BACKGROUND: We previously demonstrated that assessment of the duration of AKI, in addition to magnitude of rise in creatinine alone, adds prognostic information for long-term survival. We evaluated whether post-operative kidney injury biomarkers in urine collected immediately after cardiac surgery associate with duration of serum creatinine elevation. METHODS: We studied 1199 adults undergoing cardiac surgery in a prospective cohort study (TRIBE-AKI) and examined the association between the levels of five urinary biomarkers individually at 0-6 hours after surgery: interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid binding protein (L-FABP) and albumin with duration of serum creatinine-based AKIN criteria for AKI (0 (no AKI), 1-2, 3-6, ≥7 days)...
2016: PloS One
Rojo A Ratsimandresy, Mohanalaxmi Indramohan, Andrea Dorfleutner, Christian Stehlik
Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease (IBD) and increases the risk for colorectal cancer. Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice. However, the inflammasome sensor absent in melanoma 2 (AIM2) protects against colorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways. Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined...
August 15, 2016: Cellular & Molecular Immunology
P Przybylowski, G Wasilewski, E Koc-Żórawska, J Malyszko
BACKGROUND: Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion, and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Its elevated level is connected with endothelial activation, neovascularization, and inflammation or carcinogenesis. METHODS: The level of serum endocan among 131 heart transplant recipients on 3-drug immunosuppression (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, steroid) in correlation with other markers of endothelial damage was determined...
June 2016: Transplantation Proceedings
Tuuli Ahlstrand, Heidi Tuominen, Arzu Beklen, Annamari Torittu, Jan Oscarsson, Raija Sormunen, Marja T Pöllänen, Perttu Permi, Riikka Ihalin
Intrinsically disordered proteins (IDPs) do not have a well-defined and stable three-dimensional fold. Some IDPs can function as either transient or permanent binders of other proteins and may interact with an array of ligands by adopting different conformations. A novel outer membrane lipoprotein, bacterial interleukin receptor I (BilRI) of the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans binds a key gatekeeper proinflammatory cytokine interleukin (IL)-1β. Because the amino acid sequence of the novel lipoprotein resembles that of fibrinogen binder A of Haemophilus ducreyi, BilRI could have the potential to bind other proteins, such as host matrix proteins...
July 26, 2016: Virulence
Emmanuela M Anandarajah, Dana Ditgen, Jan Hansmann, Klaus D Erttmann, Eva Liebau, Norbert W Brattig
The secreted protein acidic and rich in cysteine (SPARC), found in the excretory/secretory products of Strongyloides ratti, is most strongly expressed in parasitic females. Since SPARC proteins are involved in the modulation of cell-matrix interactions, a role of the secreted S. ratti SPARC (Sr-SPARC) in the manifestation of the parasite in the host's intestine is postulated. The full-length cDNA of Sr-SPARC was identified and the protein was recombinantly expressed. The purified protein was biologically active, able to bind calcium, and to attach to mucosa-associated human cells...
June 2016: Molecular and Biochemical Parasitology
Yejin Kim, Tae Wan Kim, Yun Seong Park, Eui Man Jeong, Dong-Sup Lee, In-Gyu Kim, Hum Chung, Young-Il Hwang, Wang Jae Lee, Hyeong Gon Yu, Jae Seung Kang
IL-22 is a pro- and anti-inflammatory cytokine that is mainly produced by T cells and NK cells. Recent studies have reported the increased number of IL-22 producing T cells in patients with autoimmune noninfectious uveitis; however, the correlation between IL-22 and uveitis remains unclear. In this study, we aimed to determine the specific role of IL-22 and its receptor in the pathogenesis of uveitis. Serum concentration of IL-22 was significantly increased in uveitis patients. IL-22Rα was expressed in the retinal pigment epithelial cell line, ARPE-19...
2016: PloS One
Susan Thrane, Christoph M Janitzek, Sungwa Matondo, Mafalda Resende, Tobias Gustavsson, Willem Adriaan de Jongh, Stine Clemmensen, Will Roeffen, Marga van de Vegte-Bolmer, Geert Jan van Gemert, Robert Sauerwein, John T Schiller, Morten A Nielsen, Thor G Theander, Ali Salanti, Adam F Sander
BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP components...
2016: Journal of Nanobiotechnology
Chengshui Chen, Lin Shi, Yuping Li, Xiangdong Wang, Shuanying Yang
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics...
June 2016: Cell Biology and Toxicology
Dongmei Wang, Yaping Xue, Yanhua Yan, Minjie Lin, Jiajia Yang, Jianzhong Huang, Yanguo Hong
The rodent Mas-related gene (Mrg) receptor subtype C has been demonstrated to inhibit pathological pain. This study investigated the mechanisms underlying the reversal of pain hypersensitivity by the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) in a rat model of L5 spinal nerve ligation (SNL). Intrathecal (i.t.) administration of BAM8-22 (0.1-10nmol) attenuated mechanical allodynia in a dose-dependent manner on day 10 after SNL. The antiallodynia effect of BAM8-22 was abolished by MrgC receptor antibody, but not by naloxone...
July 2016: Neurobiology of Disease
Sang Jin Lee, Donghyun Lee, Taek Rim Yoon, Hyung Keun Kim, Ha Hyeon Jo, Ji Sun Park, Jun Hee Lee, Wan Doo Kim, Il Keun Kwon, Su A Park
UNLABELLED: For tissue engineering, a bio-porous scaffold which is applied to bone-tissue regeneration should provide the hydrophilicity for cell attachment as well as provide for the capability to bind a bioactive molecule such as a growth factor in order to improve cell differentiation. In this work, we prepared a three-dimensional (3D) printed polycaprolactone scaffold (PCLS) grafted with recombinant human bone morphogenic protein-2 (rhBMP2) attached via polydopamine (DOPA) chemistry...
August 2016: Acta Biomaterialia
A-w Shao, H Sun, Y Geng, Q Peng, P Wang, J Chen, T Xiong, R Cao, J Tang
Inducing senescence in cancer cells is an effective approach to suppress cancer growth, and it contributes significantly to the efficacy of therapeutic drugs. Previous studies indicated that transcription factors NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) and C/EBPβ (CCAAT/enhancer-binding protein-β) play a critical role in the establishment of senescence by upregulating proinflammatory cytokines, notably interleukin-6 (IL-6) and interleukin-8 (IL-8). However, it is not clear how these two factors are activated in response to senescence-inducing stimuli and subsequently regulate gene transcription...
May 2016: Cell Death and Differentiation
Zhou Zhou, Ming-Jiang Xu, Bin Gao
Hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. Hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. These proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide signaling, and the coagulation factor fibrinogen that activates innate immunity...
May 2016: Cellular & Molecular Immunology
Peter J Morrison, Sarah J Ballantyne, Sandy J Macdonald, John W J Moore, David Jenkins, Jill F Wright, Lynette A Fouser, Marika C Kullberg
Type 17 helper T-cell cytokines have been implicated in the pathogenesis of inflammatory bowel disease, a chronic condition affecting the gastrointestinal tract, but information regarding their contribution to pathology in different regions of the gut is lacking. By using a murine model of bacteria-induced typhlocolitis, we investigated the role of IL-17A, IL-17F, and IL-22 in cecal versus colonic inflammation. Cecal, but not colonic, pathology in C57BL/6 mice inoculated with Helicobacter hepaticus plus anti-IL-10 receptor (IL-10R) monoclonal antibody was exacerbated by co-administration of anti-IL-17A monoclonal antibody, suggesting a disease-protective role for IL-17A in the cecum...
December 2015: American Journal of Pathology
J C Martin, G Bériou, M Heslan, C Bossard, A Jarry, A Abidi, P Hulin, S Ménoret, R Thinard, I Anegon, C Jacqueline, B Lardeux, F Halary, J-C Renauld, A Bourreille, R Josien
Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel diseases (IBDs), are characterized by high levels of IL-22 production. Rodent studies revealed that this cytokine is protective during colitis but whether this is true in IBDs is unclear. We show here that levels of the soluble inhibitor of IL-22, interleukin 22-binding protein (IL-22BP), are significantly enhanced during IBDs owing to increased numbers of IL-22BP-producing eosinophils, that we unexpectedly identify as the most abundant source of IL-22BP protein in human gut...
March 2016: Mucosal Immunology
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