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Interferon regulatory factor

Andrew D Cook, Ming-Chin Lee, Reem Saleh, Hsu-Wei Khiew, Anne D Christensen, Adrian Achuthan, Andrew J Fleetwood, Derek C Lacey, Julia E Smith, Irmgard Förster, John A Hamilton
TNF and granulocyte macrophage-colony stimulating factor (GM-CSF) have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. We previously identified a new GM-CSF→JMJD3 demethylase→interferon regulatory factor 4 (IRF4)→CCL17 pathway that is active in monocytes/macrophages in vitro and important for inflammatory pain, as well as for arthritic pain and disease. Here we provide evidence for a nexus between TNF and this pathway, and for TNF and GM-CSF interdependency...
March 22, 2018: JCI Insight
Lauren D Aarreberg, Courtney Wilkins, Hilario J Ramos, Richard Green, Michael A Davis, Kwan Chow, Michael Gale
Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV) in vivo Here we utilized ex vivo global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response...
March 20, 2018: MBio
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
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
Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A Ashkar, Michel J Tremblay, Dawn Me Bowdish, Charu Kaushic
More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection...
March 19, 2018: Cellular & Molecular Immunology
Wei Tian, Jun Ma, Ruyi Shi, Chongren Ren, Jiefeng He, Haoliang Zhao
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. γδ T cells have been revealed to be promising candidates for immunotherapy in patients with HCC. However, the use of these cells in clinical practice has been demonstrated to be challenging. In the present study, γδ T cells isolated from the peripheral blood of patients with HCC (n=83) and healthy donors (n=15) were characterized. Flow cytometry was used to analyze the proportion, phenotype, tumor-killing capacity and cytokine secretion of regulatory T cells (Tregs) and γδ T17 cells in peripheral blood samples prior to and following amplification...
April 2018: Oncology Letters
Zilong Hu, Shidong Hu, Youjun Wu, Songyan Li, Changzheng He, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As2 O3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro ...
April 2018: Oncology Letters
Jaana Rysä, Heikki Tokola, Heikki Ruskoaho
Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by mechanical stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P < 0.05) genes in response to 1, 4, 12, 24, and 48 hours of cyclic mechanical stretch...
March 16, 2018: Scientific Reports
Peng You, Ning Chen, Lin Su, Tao Peng, Guodong Chen, Yulan Liu
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
April 2018: Experimental and Therapeutic Medicine
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
Jeong-Eun Kwon, Seon-Yeong Lee, Hyeon-Beom Seo, Young-Mee Moon, Jun-Geol Ryu, Kyung-Ah Jung, Joo-Yeon Jhun, Jin-Sil Park, Soo-Seok Hwang, Joo-Myeong Kim, Gap Ryol Lee, Sung-Hwan Park, Mi-La Cho
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that functions in cooperation with various cofactors to regulate gene expression. In the immune system, YY1 enhances cytokine production and T helper (Th) 2 effector cell differentiation, resulting in the activation of inflammation. However, no studies have reported the role of YY1 in Th17 cell regulation, which is implicated in rheumatoid arthritis (RA). We investigated the expression of YY1 in Th17 cells in vitro and revealed increased levels of YY1 mRNA and protein...
March 12, 2018: Immunology Letters
Dongjiao Wang, Sujun Gao, Jintong Chen, Yinghua Zhao, Yuxue Jiang, Xiao Chu, Xiaohua Wang, Ning Liu, Tianxue Qin, Qing Yi, Ying Yue, Siqing Wang
Interleukin-33 (IL-33) is a potent contributor to antiviral immune responses and antitumor immunity. We recently discovered that IL-33 is overexpressed in dectin-1-activated dendritic cells (DCs). However, mechanisms of dectin-1-induced IL-33 expression in DCs remain elusive. Curdlan, an agonist of dectin-1, was used to mature DCs in this study. We found that dectin-1-induced IL-33 expression in DCs relies on Syk and Raf-1 pathways. By using nuclear factor (NF)-κB inhibitors, we also found that dectin-1-induced IL-33 expression relies on NF-κB signaling...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mathew A Cherian, Sydney Olson, Hemalatha Sundaramoorthi, Kitra Cates, Xiaogang Cheng, John Harding, Andrew Martens, Grant A Challen, Manoj Tyagi, Lee Ratner, Daniel Rauch
The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL...
March 14, 2018: Journal of Biological Chemistry
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Peter Moritz Becher, Svenja Hinrichs, Nina Fluschnik, Jan K Hennigs, Karin Klingel, Stefan Blankenberg, Dirk Westermann, Diana Lindner
Heart failure (HF) is a leading cause of morbidity and mortality in the western world. Although optimal medical care and treatment is widely available, the prognosis of patients with HF is still poor. Toll-like receptors (TLRs) are important compartments of the innate immunity. Current studies have identified TLRs as critical mediators in cardiovascular diseases. In the present study, we investigated the involvement of TLRs and interferon (IFN) regulatory factors (IRFs) in different experimental HF models including viral myocarditis, myocardial ischemia, diabetes mellitus, and cardiac hypertrophy...
2018: PloS One
Wan Peng, Yan Sun, Gao-Fei Li, Liang-Ge He, Ruo-Zhu Li, Yao-Si Liang, Xu Ding, Xue Yu, Yong Zhang, Hao-Ran Lin, Dan-Qi Lu
Interferon gamma (IFNγ) is a Th1 cytokine that is critical for innate and adaptive immunity. Toll-like receptors (TLRs) signaling pathways are critical in early host defense against invading pathogens. miR-146a has been reported to participate in the regulation of host immunity. The known mechanisms of integrations between the IFNγ and TLR signaling pathways are incompletely understood, especially in teleosts. In this study, orange-spotted grouper ( Epinephelus coioides ) IFNγ1 and IFNγ2, their biological activities, especially their involvements in TLR pathway, were explored...
2018: Frontiers in Endocrinology
Meysam Nasiri, Mohammad-Hossein Karimi, Negar Azarpira, Iraj Saadat
OBJECTIVES: Toll-like receptors and downstream signal transduction pathways play pivotal roles in induction of inflammation, which is crucial for liver injury and regeneration. MATERIALS AND METHODS: Using a mouse model of partial hepatic ischemia-reperfusion injury followed by a 28-day time course for liver repair and regeneration, we assessed gene expression levels for Toll-like receptors, myeloid differentiation primary response 88, TIR-domain-containing adapter-inducing interferon-β, nuclear factor κB, interferon regulatory factors, tumor necrosis factor-α, and interleukins 1β and 6 at days 1, 4, 7, 14, and 28 after reperfusion in liver and blood cells by quantitative polymerase chain reaction...
March 9, 2018: Experimental and Clinical Transplantation
M Nasiri, B Geramizadeh, S H Nabavizadeh, S A Male-Hosseini, M H Karimi, I Saadat
Background: Interferon regulatory factors (IRFs) can play a critical role in the regulation of many facets of innate and adaptive immune responses through transcriptional activation of type I interferons, other proinflammatory cytokines, and chemokines. However, their roles in transplantation immunity still remain to be elucidated. Objective: To evaluate the time course of mRNA expression of all 9 members of IRFs family of transcription factors during liver allograft acute rejection...
2018: International Journal of Organ Transplantation Medicine
Masakatsu Yamashita, Makoto Kuwahara
Although Bach2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) plays an important role in regulating Th2 cell differentiation and type-2 immune responses, the underlying molecular mechanisms remain unclear. Our current studies demonstrate that Bach2 associates with Batf (basic leucine zipper transcription factor ATF-like) family transcription factors and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the interferon regulatory factor 4 (Irf4)-containing Batf complex to activator protein 1 (AP-1) motifs in the Th2 cytokine gene locus and suppresses Th2 cytokine production and/or Th2 cell differentiation...
February 24, 2018: International Immunology
Almin I Lalani, Sining Zhu, Samantha Gokhale, Juan Jin, Ping Xie
Purpose of Review: This review presents an overview of the current knowledge of TRAF molecules in inflammation with an emphasis on available human evidence and direct in vivo evidence of mouse models that demonstrate the contribution of TRAF molecules in the pathogenesis of inflammatory diseases. Recent Findings: The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic proteins was initially identified as signaling adaptors that bind directly to the intracellular domains of receptors of the TNF-R superfamily...
February 2018: Current Pharmacology Reports
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