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Noah E Kelm, Ziwen Zhu, Vivi A Ding, Huaping Xiao, Mark R Wakefield, Qian Bai, Yujiang Fang
Interleukin-29 (IL-29) is a new member of the recently discovered interferon λ (IFNλ) family. It is produced predominantly by maturing dendritic cells and macrophages. It has been implicated in numerous immunological responses and has shown antiviral activity similar to the Type I interferons, although its target cell population is more limited than the Type I interferons. In recent years, the role of IL-29 in the pathogenesis of various cancers has also been extensively studied. In this review, we will discuss the recent advances of IL-29 in immunological processes and the pathogenesis of various cancer...
October 2016: Critical Reviews in Oncology/hematology
J da Silva, C Hilzendeger, C Moermans, F Schleich, M Henket, T Kebadze, P Mallia, M R Edwards, S L Johnston, R Louis
BACKGROUND: Interferons play an important role in innate immunity. Previous studies report deficiency in virus induction of interferon (IFN)-α, IFN-β and IFN-λ in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection. OBJECTIVE: The aim of this study was to investigate whether the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation...
September 13, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Dilek Arpaci, Sevim Karakas Celik, Murat Can, Gunes Cakmak Genc, Fatih Kuzu, Mustafa Unal, Taner Bayraktaroglu
Hashimoto's thyroiditis (HT) is thought to result from decreased T helper type 2 (Th2) responses, leading to the progressive destruction of thyrocytes. IFN-λ1, -λ2, and -λ3 (also known as IL-29, IL-28A, and IL-28B, respectively) are recently described members of the IFN-λ family and have been shown to decrease the production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in HT remain unknown. The purpose of this study was to examine whether IL29 and IL28B gene polymorphisms are susceptibility genes for the development of HT...
October 2016: Immunological Investigations
Benjamin Krämer, Claudia Finnemann, Beatriz Sastre, Philipp Lutz, Andreas Glässner, Franziska Wolter, Felix Goeser, Pavlos Kokordelis, Dominik Kaczmarek, Hans-Dieter Nischalke, Christian P Strassburg, Ulrich Spengler, Jacob Nattermann
BACKGROUND: Immuno-genetic studies suggest a functional link between NK cells and λ-IFNs. We recently showed that NK cells are negative for the IFN-λ receptor IFN-λR1 and do not respond to IFN-λ, suggesting a rather indirect association between IL-28B genotype and NK cell activity. METHODS: A total of 75 HCV(+) patients and 67 healthy controls were enrolled into this study. IL-28B (rs12979860) and IFNL-4 (rs368234815) genotypes were determined by rtPCR. Total PBMC, monocytes, and NK cells were stimulated with IL-29, the TLR-7/8 agonist R848, or a combination of both...
2016: PloS One
K Hasegawa, M Tagawa, K Takagi, H Tsukamoto, Y Tomioka, T Suzuki, Y Nishioka, T Ohrui, M Numasaki
Interleukin (IL)-28A/interferon (IFN)-λ2 and IL-29/IFN-λ1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, we constructed an adenovirus vector expressing either IL-28A/IFN-λ2 (AdIL-28A) or IL-29/IFN-λ1 (AdIL-29) to evaluate the therapeutic properties of intratumoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections of either AdIL-28A or AdIL-29 when compared with AdNull...
August 2016: Cancer Gene Therapy
Lin Qu, Kosuke Murakami, James R Broughman, Margarita K Lay, Susana Guix, Victoria R Tenge, Robert L Atmar, Mary K Estes
UNLABELLED: Human noroviruses (HuNoVs), named after the prototype strain Norwalk virus (NV), are a leading cause of acute gastroenteritis outbreaks worldwide. Studies on the related murine norovirus (MNV) have demonstrated the importance of an interferon (IFN) response in host control of virus replication, but this remains unclear for HuNoVs. Despite the lack of an efficient cell culture infection system, transfection of stool-isolated NV RNA into mammalian cells leads to viral RNA replication and virus production...
October 1, 2016: Journal of Virology
P Parroche, G Roblot, F Le Calvez-Kelm, I Tout, M Marotel, M Malfroy, G Durand, J McKay, M Ainouze, C Carreira, O Allatif, A Traverse-Glehen, M Mendiola, J J Pozo-Kreilinger, C Caux, M Tommasino, N Goutagny, U A Hasan
Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar...
2016: Oncogenesis
Lingxiao Xu, Qiuyue Peng, Wenhua Xuan, Xiaoke Feng, Xiangqing Kong, Miaojia Zhang, Wenfeng Tan, Meilang Xue, Fang Wang
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC)...
2016: Mediators of Inflammation
Clarissa Hilzendeger, Jane da Silva, Monique Henket, Florence Schleich, Jean Louis Corhay, Tatiana Kebadze, Michael R Edwards, Patrick Mallia, Sebastian L Johnston, Renaud Louis
BACKGROUND: Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients. METHODS: Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects. Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR)...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Pablo Ramon Gualberto Cardoso, Emerson Vasconcelos de Andrade Lima, Mariana Modesto de Andrade Lima, Moacyr Jesus Barreto de Melo Rêgo, Claudia Diniz Lopes Marques, Ivan da Rocha Pitta, Angela Luzia Branco Pinto Duarte, Maira Galdino da Rocha Pitta
Psoriasis is a common, enigmatic, and recurrent disease. The precise etiology and pathogenesis of psoriasis are still unclear. Psoriasis has been treated as an inflammatory disorder related to an underlying Th1/Th17-dominated immune response. Interleukins are involved in the development of psoriasis lesions through Th-17-associated inflammation. Th1 and Th17 cytokines are found in skin lesions and in the peripheral blood of psoriasis patients. We sought to analyze serum levels of IL-1-β, IL-8, IL-9, IL-27, IL-29, IL-35, IFN-γ, TNF and TGF-β in patients with psoriasis and healthy control volunteers...
March 1, 2016: European Cytokine Network
Hua Pei, Li Zuo, Jing Ma, Lili Cui, Fangfang Yu, Yingzi Lin
A cell model is critical for studying the molecular mechanisms of dengue virus 2 (DENV-2) invasions and cell bioactivity can be easily affected by the substrate matrix. Tissue culture plastic (TCP) and polyacrylamide hydrogel (PAMH) are two kinds of matrices widely used for cells. The effects of different matrices on the cultured cells with DENV-2 invasion remain unknown. To address the issue, the effects of TCP and PAMH were explored in primary human umbilical vein endothelial cells (HUVECs) with DENV-2 invasion...
July 2016: Journal of Medical Virology
Khanit Sa-Ngiamsuntorn, Adisak Wongkajornsilp, Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Wasun Chantratita, Suradej Hongeng
BACKGROUND: Hepatitis C virus (HCV) could induce chronic liver diseases and hepatocellular carcinoma in human. The use of primary human hepatocyte as a viral host is restrained with the scarcity of tissue supply. A culture model restricted to HCV genotype 2a (JFH-1) has been established using Huh7-derived hepatocyte. Other genotypes including the wild-type virus could not propagate in Huh7, Huh7.5 and Huh7.5.1 cells. METHODS: Functional hepatocyte-like cells (HLCs) were developed from normal human iPS cells as a host for HCV infection...
2016: Virology Journal
Michael R Edwards, Fabrizio Facchinetti, Maurizio Civelli, Gino Villetti, Sebastian L Johnston
Respiratory virus infections precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations, with most exacerbations due to rhinovirus infection. Both asthma and COPD exacerbations are not well controlled by steroid therapies, and there is a much research interest in finding improved therapies or combinations of therapies for controlling exacerbations. CHF6001 is a new, inhaled highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor. Using in vitro human bronchial epithelial cells (BEAS-2B), we investigated the potential anti-inflammatory effects of CHF6001 on rhinovirus (RV1B)-induced cytokines...
February 2016: Pharmacology Research & Perspectives
Anne-Mieke J W Haasnoot, Jonas J W Kuiper, Sanne Hiddingh, Peter A W J F Schellekens, Wilco de Jager, Saskia M Imhof, Timothy R D J Radstake, Joke H de Boer
OBJECTIVE: Childhood uveitis is a vision-threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis is poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor [AqH]) and serum from children with JIA-associated uveitis and common childhood uveitis to identify potential biomarkers and investigate the ocular microenvironment of this sight-threatening eye disease. METHODS: AqH (n = 73) and paired serum (n = 66) samples were analyzed for 51 soluble mediators of inflammation by multiplex immunoassay...
July 2016: Arthritis & Rheumatology
Tatsuo Kanda, Shingo Nakamoto, Shuang Wu, Masato Nakamura, Xia Jiang, Yuki Haga, Reina Sasaki, Osamu Yokosuka
Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs)...
September 28, 2015: Journal of Clinical and Translational Hepatology
Ellen Witte, Georgios Kokolakis, Katrin Witte, Katarzyna Warszawska, Markus Friedrich, Demetrios Christou, Stefan Kirsch, Wolfram Sterry, Hans-Dieter Volk, Robert Sabat, Kerstin Wolk
UNLABELLED: Psoriasis is considered as a model for chronic immune-mediated disorders. Th17-cells are pivotal players in those diseases. Recently, we demonstrated that Th17-cells produce interleukin (IL)-29 and that IL-29 is highly present in psoriatic lesions. Whether IL-29, with its action on epithelial cells and melanocytes, contributes to psoriasis pathogenesis, was unknown so far. Analysis of IL-29-treated human keratinocytes revealed induction of the chemokines CXCL10, CXCL11, and, to a much lesser extent, CXCL9...
April 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Wei Chen, Rong Zhu, Chunlei Ge, Yuan Lu, Liyun Li, Fei Li, Minchen Wu
To explore the anti-tumor proliferation activity of human interleukin-29 (hIL-29) variant and based on bioinformatics analyzed data of hIL-29, a mutant gene hIL-29(mut33,35) was amplified by site-directed mutagenesis and megaprimer PCR. The hIL-29(mut33,35) was inserted into an eukaryotic expression plasmid pPIC9K and successfully expressed in Pichia pastoris GS115. A recombinant variant protein (rhIL-29(mut33,35)) was purified from the ferment supernatant of the engineering GS115. To observe the antineoplastic activity of the variant rhIL-29(mut33,35), a CCK-8 reagent was used to detect the anti-proliferation effect...
May 2015: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Rémi Villenave, Lindsay Broadbent, Isobel Douglas, Jeremy D Lyons, Peter V Coyle, Michael N Teng, Ralph A Tripp, Liam G Heaney, Michael D Shields, Ultan F Power
UNLABELLED: Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well-differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide...
December 2015: Journal of Virology
Ajita Meenawat, Vivek Govila, Sudhir Goel, Sunil Verma, Karan Punn, Vivek Srivastava, Rameshwar Shantaram Dolas
BACKGROUND AND OBJECTIVE: Smoking is an important environmental risk factor involved in the causation and progression of periodontal disease. Smoking can impair various components of the host immune response and immune system. The virulence factors of periodontal pathogens stimulate inflammatory cytokine expression by mononuclear cells. IL-1β is the key mediator involved in the pathogenesis and disease progression. Therefore, whole gingival biopsy samples are assessed for this increased expression of IL-1...
July 2015: Journal of Indian Society of Periodontology
Xue Wang, Zi-Jing Song, Xin He, Run-Qi Zhang, Chun-Feng Zhang, Fei Li, Chong-Zhi Wang, Chun-Su Yuan
Colorectal cancer is the third most common malignant tumor with high morbidity and mortality. To evaluate the antitumor effect of genkwanin on colorectal cancer enhanced by western high-fat diet, we investigated the activity of genkwanin on HT-29 and SW-480 human colorectal cancer lines in vitro and on the APC(Min/+) mice in vivo. In a cell culture system, six different inflammatory cytokines obviously stimulated two cancer cells growth in a concentration-dependent manner, while genkwanin significantly inhibited HT-29 and SW-480 human colorectal cancer cells proliferation and inflammatory cytokine IL-8 secretion...
December 2015: International Immunopharmacology
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