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Interferon promoter stimulator

Yanzhao Chen, Baihai Jiao, Min Yao, Xuezhen Shi, Zhebin Zheng, Shilin Li, Limin Chen
Interferon stimulated (sensitive) genes (ISGs) are the effector molecules downstream of type I/III interferon (IFN) signaling pathways in host innate immunity. ISG12a can be induced by IFN-α. Although ISG12a has been reported to inhibit the replication of HCV, the exact mechanism remains to be determined. In this study, we investigated the possible mechanisms of ISG12a anti- HCV property by exploring the production of type I IFN and the activation of Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway, apoptosis and autophagy in Huh7...
October 21, 2016: Virus Research
Daniel A Patten, Garrick K Wilson, Dalan Bailey, Robert K Shaw, Sirpa Jalkanen, Marko Salmi, Antal Rot, Christopher J Weston, David H Adams, Shishir Shetty
: The recruitment of lymphocytes via the hepatic sinusoidal channels and positioning within liver tissue is a critical event in the development and persistence of chronic inflammatory liver diseases. The hepatic sinusoid is a unique vascular bed lined by hepatic sinusoidal endothelial cells (HSEC), a functionally and phenotypically distinct sub-population of endothelial cells. Using flow based adhesion assays to study the migration of lymphocytes across primary human HSEC, we found that lymphocytes enter into HSEC, confirmed by electron microscopy demonstrating clear intracellular localization of lymphocytes in vitro and by studies in human liver tissues...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jing Xue, Qinglan Zhao, Vishal Sharma, Linh P Nguyen, Yvonne N Lee, Kim L Pham, Mouad Edderkaoui, Stephen J Pandol, Walter Park, Aida Habtezion
BACKGROUND & AIMS: Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of CP. METHODS: We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4+ T cells; levels of interleukin-22 (IL22) were measured by ELISA and smoking histories were collected...
October 18, 2016: Gastroenterology
J R Teijaro
Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term interferon has been synonymous with inhibition of virus replication. While the antiviral properties of type 1 interferon (IFN-I) are undeniable, recent studies have reported expanding and somewhat unexpected roles of IFN-I signaling during both acute and persistent viral infections. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses and recruitment of inflammatory innate immune cell populations during acute respiratory viral infections...
2016: Advances in Immunology
Erica L Heipertz, Jourdan Harper, Wendy E Walker
IFN regulatory factor (IRF)3 plays a detrimental role in the cecal ligation and puncture (CLP) mouse model of sepsis. However, it is unclear which pathway activates IRF3 in this context. In this report we investigate two pathways that activate IRF3: the Stimulator of Interferon Genes (STING) pathway (which senses cytosolic DNA) and the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway (which sense dsRNA and LPS via Toll-like receptor (TLR) 3 and 4). Initially, we examine the impact of these pathways using a severe CLP model (∼90% mortality)...
October 17, 2016: Shock
Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
PURPOSE OF REVIEW: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments. RECENT FINDINGS: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-1 are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance...
October 13, 2016: Current Opinion in Allergy and Clinical Immunology
Tomohiro Watanabe, Kouhei Yamashita, Masatoshi Kudo
An increased number of clinicopathological studies on autoimmune pancreatitis, cholangitis, and sialoadenitis have led to the recognition of immunoglobulin G4-related disease (IgG4-RD) as a novel disorder, characterized by elevated levels of serum IgG4 and infiltration of IgG4-expressing plasma cells in the affected organs. Although the immunological background associated with the development of IgG4-RD remains poorly understood, recent studies have suggested involvement of the innate immune response in its pathogenesis...
October 16, 2016: Current Topics in Microbiology and Immunology
Rebecca Baum, Shruti Sharma, Jason M Organ, Christopher Jakobs, Veit Hornung, David B Burr, Ann Marshak-Rothstein, Katherine A Fitzgerald, Ellen M Gravallese
OBJECTIVE: Cytosolic DNA sensors detect microbial DNA and promote type I interferon and pro-inflammatory cytokine production through the adaptor stimulator of interferon genes (STING) to resolve infection. Endogenous DNA also engages the STING pathway, contributing to autoimmune disease. We identified a novel role for STING in bone in arthritic DNase II/IFNaR double deficient (DKO) mice, and sought to define the bone phenotype in these mice and to address mechanism. METHODS: Bone parameters were evaluated in DKO, STING/DNaseII/IFNaR triple deficient and control mice by microcomputed tomography and histomorphometry...
October 14, 2016: Arthritis & Rheumatology
Li Li, Yan Ma, Shuang Liu, Jin Zhang, Xin-Yan Xu
Human papillomavirus (HPV)-specific CD8(+) T cells are present in HPV-infected cervical cancer patients and have demonstrated potent antitumor properties. However, these cells cannot control tumor progression in most patients. To investigate the underlying mechanisms involved in suppressing or promoting CD8(+) T cell functions, we focused on interleukin 10 (IL-10), a pleiotropic cytokine with controversial roles in antitumor immunity. We found that compared to healthy controls, circulating CD8(+) T cells in HPV 16-infected cervical cancer patients expressed significantly higher levels of IL-10...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Maria Pannell, Dominika Labuz, Melih Ö Celik, Jacqueline Keye, Arvind Batra, Britta Siegmund, Halina Machelska
BACKGROUND: During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. METHODS: Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4...
October 7, 2016: Journal of Neuroinflammation
Xiangyu Yao, Jian Wu, Meng Lin, Wenxiang Sun, Xiao He, Channe Gowda, Silvia Bolland, Carole A Long, Rongfu Wang, Xin-Zhuan Su
Both type I interferon (IFN-I) and CD40 play a significant role in various infectious diseases, including malaria and autoimmune disorders. CD40 is mostly known to function in adaptive immunity, but previous observations of elevated CD40 levels early after malaria infection of mice led us to investigate its roles in innate IFN-I responses and disease control. Using a Plasmodium yoelii nigeriensis N67 and C57BL/6 mouse model, we showed that infected CD40-/- mice had reduced STING and serum IFN-β levels day-2 post infection, higher day-4 parasitemia, and earlier deaths...
October 2016: PLoS Pathogens
Brooke A Napier, Sky W Brubaker, Timothy E Sweeney, Patrick Monette, Greggory H Rothmeier, Nina A Gertsvolf, Andreas Puschnik, Jan E Carette, Purvesh Khatri, Denise M Monack
Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11-dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9-mediated genome-wide screen, we identified novel mediators of caspase-11-dependent cell death...
October 3, 2016: Journal of Experimental Medicine
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
October 3, 2016: Glia
Haiyan S Li, Chengwen Liu, Yichuan Xiao, Fuliang Chu, Xiaoxuan Liang, Weiyi Peng, Jianhua Hu, Sattva S Neelapu, Shao-Cong Sun, Patrick Hwu, Stephanie S Watowich
Despite the potent ability of dendritic cells (DCs) to stimulate lymphocyte responses and host immunity, granulocyte-macrophage colony-stimulating factor-derived DCs (GM-DCs) used as antitumor vaccines have demonstrated relatively modest success in cancer immunotherapy. We found that injecting GM-DCs into melanoma tumors in mice, or culturing GM-DCs with melanoma-secreted cytokines or melanoma-conditioned medium, rapidly suppressed DC-intrinsic expression of the gene encoding inhibitor of differentiation 2 (ID2), a transcriptional regulator...
2016: Science Signaling
Jiaoli Wang, Weiguo Zhu, Yinghu Chen, Zhendong Lin, Shenglin Ma
Predominant T helper (Th)2 and impaired Th1 cell polarization has a crucial role in the development of asthma. Cluster of differentiation (CD)38 is associated with the increased release of interleukin (IL)‑12 from dendritic cells (DCs) and DC‑induced Th1 cell polarization. However, whether CD38 expression affects DC function in asthma development remains unknown. In the current study, adenoviruses were constructed containing the murine CD38 gene. Overexpression of CD38 protein level in DCs induced from bone‑marrow derived DCs (BMDCs) by recombinant mouse granulocyte macrophage colony‑stimulating factor and IL‑4 was achieved through 24 h adenovirus infection...
September 21, 2016: Molecular Medicine Reports
Robert G Schaut, Tara L Grinnage-Pulley, Kevin J Esch, Angela J Toepp, Malcolm S Duthie, Randall F Howard, Steven G Reed, Christine A Petersen
Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4(+) T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum-specific interferon gamma (IFNγ) driven-Th1 responses become dampened and a state of immune exhaustion established...
October 17, 2016: Vaccine
Ryo Hayakari, Tomoh Matsumiya, Fei Xing, Hidemi Yoshida, Makoto Hayakari, Tadaatsu Imaizumi
The cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I), which is also known as an IFN-stimulated gene (ISG), senses viral RNA to activate antiviral signaling. It is therefore thought that RIG-I is regulated in a STAT1-dependent manner. Although RIG-I-mediated antiviral signaling is indispensable for the induction of an appropriate adaptive immune response, the mechanism underlying the regulation of RIG-I expression remains elusive. Here, we examined the direct regulation of RIG-I expression by interferon regulatory factor 3 (IRF-3), which is an essential molecule for antiviral innate immunity...
2016: PloS One
Johan Frostegård, Yong Zhang, Jitong Sun, Keqiang Yan, Anquan Liu
BACKGROUND: Activated T cells and dendritic cells (DCs) are colocalized in atherosclerotic plaques in association with plaque rupture. Oxidized low-density lipoprotein (oxLDL) promotes immune activation and inflammation. We studied the effects of statins (atorvastatin and simvastatin) on human DC maturation and T-cell activation. METHODS AND RESULTS: Human peripheral blood monocytes were differentiated to DCs and stimulated with oxLDL. T cells were isolated from carotid endarterectomy specimens from patients undergoing carotid endarterectomy or from healthy individuals...
September 2016: Journal of the American Heart Association
Ragab M Fereig, Yoshifumi Nishikawa
Toxoplasmosis remains a life-threatening infection of humans and various domestic and wild animals worldwide. It is caused by the obligatory intracellular protozoan parasite Toxoplasma gondii. Peroxiredoxins (Prxs) are a family of antioxidant enzymes that protect cells from oxidative stress from hydroperoxides. In the recent years, several studies have reported the potential use of T. gondii-derived enzymes in triggering protective immunity against T. gondii infection. Therefore, this study was conducted to investigate the immunogenicity and protective efficacy of TgPrx3...
December 2016: Parasitology International
Yun-Gang Lv, Li Kang, Guangyao Wu
Estrogen deficiency in postmenopausal women frequently activates osteoclasts (OC), accelerates bone resorption, and leads to osteoporosis (OP). Previous studies have demonstrated that interferon γ (IFNγ) could increase bone resorption and may be involved in postmenopausal OP. Fluorosis also increased the risk of fractures and dental fluorosis, and fluoride may enhance osteoclast formation and induce osteoclastic bone destruction in postmenopausal women, but the underlying mechanisms are as yet unknown. Here, we show that serum fluoride and IFNγ levels are negatively correlated with bone mineral density (BMD) in postmenopausal women residing in a fluorotic area...
October 14, 2016: Biochemical and Biophysical Research Communications
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