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Subir K Nagdas, Virginia P Winfrey, Gary E Olson
Nevertheless, a nonviable sperm population is present in the cauda epididymidis of many species. Degenerating spermatozoa release enzymes that could have detrimental effects on the viability of neighboring cells, and they are source of autoantigens that induce an autoimmune response if they escape the blood-epididymis barrier. Does the epididymis have specialized protective mechanism(s) to segregate the viable sperm population from defective spermatozoa? Previously, we identified a fibrinogen-like protein-2 (fgl2) that specifically binds to and polymerizes into a cocoon-like complex coating defective spermatozoa and sperm fragments...
October 9, 2016: International Journal of Biochemistry & Cell Biology
Ming Wang, Junhui Liu, Dong Xi, Xiaoping Luo, Qin Ning
BACKGROUND: Human fibrinogen-like protein 2 (hFGL2) is overexpressed in various human solid tumors and is associated with tumor growth, invasion and angiogenesis of hepatocellular carcinoma (HCC) LM6 cells. In the present study, an adenoviral vector expressing an artificial microRNA (miRNA) against hfgl2 (Ad-hfgl2-miRNA) was used to evaluate the effect of FGL2 knockdown on cell proliferation and tumor growth of HCCLM6 xenografts. METHODS: Ad-hfgl2-miRNA was constructed and its effect on hFGL2 expression and cell proliferation was analyzed...
July 2016: Journal of Gene Medicine
Stefano Giuliani, Yew-Wei Tan, Dongling Zheng, Evmorfia Petropoulou, Ali Sohail, Sarah Bradley, Justin Richards, Nigel Kennea, Yalda Jamshidi
OBJECTIVES: Coagulopathy and mesenteric thrombosis are common in premature neonates with necrotizing enterocolitis (NEC). This pilot study aimed to investigate the hypothesis that there are changes in the gene expression related to the coagulation and anticoagulation systems in NEC. METHODS: Consecutive neonates (n = 11) with NEC (Bell's stages 2-3) were recruited. Two comparison groups, matched for birth weight and corrected gestational age, were selected based on: the absence of inflammation and coagulopathy (healthy control, n = 10); or the presence of a confirmed blood infection (sepsis control, n = 12)...
March 31, 2016: Journal of Pediatric Gastroenterology and Nutrition
A Bartczak, A Chruscinski, M Mendicino, H Liu, J Zhang, W He, A Z Amir, A Nguyen, R Khattar, H Sadozai, C G Lobe, O Adeyi, M J Phillips, L Zhang, R M Gorczynski, D Grant, G A Levy
Fibrinogen-like protein 2 (FGL2) is an immunomodulatory protein that is expressed by regulatory T cells (Tregs). The objective of this study was to determine if recombinant FGL2 (rFGL2) treatment or constitutive FGL2 overexpression could promote transplant tolerance in mice. Although rFGL2 treatment prevented rejection of fully mismatched cardiac allografts, all grafts were rejected after stopping treatment. Next, we generated FGL2 transgenic mice (fgl2(Tg) ) that ubiquitously overexpressed FGL2. These mice developed normally and had no evidence of the autoimmune glomerulonephritis seen in fgl2(-/-) mice...
June 2016: American Journal of Transplantation
Kuai-Fa Fang, Zhu-Jun Chen, Meng Liu, Ping-Sheng Wu, Da-Zhi Yu
OBJECTIVE: To study the mechanism and significance of pH change in the coronary artery microthrombosis of rats. METHODS: After the sodium laurate-induced model of coronary artery microthrombosis of rats was constructed, the vascular endothelial cells were separated and then cultured in the mediums with different pH values for 24 h. Enzyme linked immunosorbent assay was used to detect the content of von Willebrand factor (vWF) in the medium; while the real-time PCR and western blot assay were used to detect the expression of fibrinogen-like protein 2 (FGL2) at the mRNA and protein level...
October 2015: Asian Pacific Journal of Tropical Medicine
Rui Long, Ya You, Wenzhu Li, Nan Jin, Shiyuan Huang, Ting Li, Kun Liu, Zhaohui Wang
AIMS: The effects of sodium tanshinone IIA sulfonate (STS) on coronary no-reflow (CNR) relevant to microvascular obstruction (MVO) remain unknown. Studies had shown that fibrinogen-like protein 2 (FGL2) expressed in microvascular endothelial cells (MECs) is a key mediator in MVO. Thus, we aimed to elucidate the roles of STS in CNR and relations between STS and FGL2. MAIN METHODS: Myocardial ischemia/reperfusion was selected to represent CNR model. The no-reflow zone and infarct area were assessed using Thioflavin S and TTC staining, and cardiac functional parameters were detected using echocardiography...
December 1, 2015: Life Sciences
Sheng Guo, Chengying Yang, Bo Diao, Xiaoyong Huang, Meihua Jin, Lili Chen, Weiming Yan, Qin Ning, Lixin Zheng, Yuzhang Wu, Yongwen Chen
Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1-/-) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality...
September 2015: PLoS Pathogens
Matthew A Care, David R Westhead, Reuben M Tooze
BACKGROUND: Cancers adapt to immune-surveillance through evasion. Immune responses against carcinoma and melanoma converge on cytotoxic effectors and IFNγ-STAT1-IRF1 signalling. Local IFN-driven immune checkpoint expression can mediate feedback inhibition and adaptive immune resistance. Whether such coupled immune polarization and adaptive resistance is generalisable to lymphoid malignancies is incompletely defined. The host response in diffuse large B-cell lymphoma (DLBCL), the commonest aggressive lymphoid malignancy, provides an empirical model...
September 11, 2015: Genome Medicine
Bruno Gottstein, Junhua Wang, Ghalia Boubaker, Irina Marinova, Markus Spiliotis, Norbert Müller, Andrew Hemphill
Epidemiological studies have demonstrated that the majority of human individuals exposed to infection with Echinococcus spp. eggs exhibit resistance to disease as shown by either seroconversion to parasite--specific antigens, and/or the presence of 'dying out' or 'aborted' metacestodes, not including hereby those individuals who putatively got infected but did not seroconvert and who subsequently allowed no development of the pathogen. For those individuals where infection leads to disease, the developing parasite is partially controlled by host immunity...
October 30, 2015: Veterinary Parasitology
Andrzej Chruscinski, Hassan Sadozai, Vanessa Rojas-Luengas, Agata Bartczak, Ramzi Khattar, Nazia Selzner, Gary A Levy
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are critical to the maintenance of immune tolerance. Treg are known to utilize a number of molecular pathways to control immune responses and maintain immune homeostasis. Fibrinogen-like protein 2 (FGL2) has been identified by a number of investigators as an important immunosuppressive effector of Treg, which exerts its immunoregulatory activity by binding to inhibitory FcγRIIB receptors expressed on antigen-presenting cells including dendritic cells, endothelial cells, and B cells...
2015: Rambam Maimonides Medical Journal
Zheng Zhenzhong, Yu Yafa, Liang Jin
Fibrinogen-like protein 2 (Fgl2) is involved in apoptosis, angiogenesis and inflammatory response. Diabetes is closely associated with apoptosis, angiogenesis and coagulation. So it allowed us to assume that Fgl2 plays an important role during the process of diabetic cardiomyopathy (DCM). In the present study, we test that the feasibility of Fgl2 as a therapeutic target for the treatment of DCM and its possible molecular mechanism involved. We found that Fgl2 gene silencing inhibits apoptosis and improves heart function of streptozotocin (STZ)-induced diabetes rats, the possible mechanism maybe that Fgl2 gene silencing reduces the tumour necrosis factor (TNF)±levels, decreases the expression of B-cell lymphoma-2 (bcl2), bcl-2-associated X (bax), toll-like receptors 4 (TLR4) and p38 mitogen-activated protein kinase (MAPK)...
2015: Bioscience Reports
Genyan Yang, W Craig Hooper
Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED)...
August 25, 2013: World Journal of Clinical Infectious Diseases
Zheng Zhengzhong, Yu Yafa, Liang Jin
Fibrinogen-like protein 2(Fgl2) is involved in apoptosis,angiogenesis andinflammatory response .Diabetes is closely associated with apoptosis,angiogenesisand coagulation.So it allowed us to assume that Fgl2 plays an important role duringthe process of diabetic cardiomyopathy. In the present study, we test that thefeasibility of Fgl2 as a therapeutic target for the treatment of diabetic cardiomyopathyand its possible molecular mechanism involved.We found that fibrinogen-like protein2 gene silencing inhibits apoptosis and improves heart function ofstreptozotocin-induced diabetes rats,the possible mechanism maybe thatfibrinogen-like protein 2 gene silencing reduces the TNF-± levels,decreases theexpression of bcl2 ,bax,TLR4,and p38 MAPK...
May 20, 2015: Bioscience Reports
Jun Yan, Ling-Yuan Kong, Jiemiao Hu, Konrad Gabrusiewicz, Denada Dibra, Xueqing Xia, Amy B Heimberger, Shulin Li
BACKGROUND: Fibrinogen-like protein 2 (FGL2) may promote glioblastoma multiforme (GBM) cancer development by inducing multiple immune-suppression mechanisms. METHODS: The biological significance of FGL2 expression was assessed using the The Cancer Genome Atlast (TCGA) glioma database and tumor lysates analysis. The therapeutic effects of an anti-Fgl2 antibody and the role of immune suppression regulation by Fgl2 were determined in immune-competent, NOD-scid IL2Rgammanull (NSG), and FcɣRIIB-/- mice (n = 3-18 per group)...
August 2015: Journal of the National Cancer Institute
Junhua Wang, Dominique A Vuitton, Norbert Müller, Andrew Hemphill, Markus Spiliotis, Oleg Blagosklonov, Denis Grandgirard, Stephen L Leib, Itay Shalev, Gary Levy, Xiaomei Lu, Renyong Lin, Hao Wen, Bruno Gottstein
BACKGROUND: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection...
May 2015: PLoS Neglected Tropical Diseases
Sheng-Juan Jin, Yan Liu, Shi-Hua Deng, Li-Hong Liao, Tu-Lian Lin, Qin Ning, Xiao-Ping Luo
Maternal intrauterine inflammation or infection is an important risk factor for neonatal cerebral white matter injury (WMI) and future neurological deficits. Activated protein C (APC), a natural anticoagulant, has been shown to exhibit anti-inflammatory, anti-apoptotic, profibrinolytic and cytoprotective activities. Recent studies have demonstrated that the novel prothrombinase, fibrinogen-like protein 2 (fgl2), contributes to the pathogenesis of a number of inflammatory diseases through the generation of fibrin...
May 2015: International Journal of Molecular Medicine
Séverine Bézie, Elodie Picarda, Laurent Tesson, Karine Renaudin, Justine Durand, Séverine Ménoret, Emmanuel Mérieau, Elise Chiffoleau, Carole Guillonneau, Lise Caron, Ignacio Anegon
We previously described that in a rat model of heart transplantation tolerance was dependent on CD8+CD45RClow Tregs that over-expressed fibrinogen-like protein 2 (FGL2)/fibroleukin. Little is known on the immunoregulatory properties of FGL2. Here we analyzed the transplantation tolerance mechanisms that are present in Lewis 1A rats treated with FGL2. Over-expression of FGL2 in vivo through adenovirus associated virus -mediated gene transfer without any further treatment resulted in inhibition of cardiac allograft rejection...
2015: PloS One
Ping Zhang, Fei Cao, Nian Xiong, Jinsha Huang, Tao Wang, Liang Shao
Cerebral ischemic-reperfusion injury as an inflammatory and microcirculation dysfunction pathological condition negatively affects the clinical outcome of stroke patients. The novel inflammatory procoagulant protein fgl2 has been reported to play a role in some inflammatory and coagulation dysregulation diseases. This study aimed to examine the relationship between fgl2 expression and infarct size in an acute cerebral ischemic-reperfusion rat model. We studied fgl2 mRNA and protein expressions in cerebral tissue and peripheral macrophages, and the expressions of several inflammatory factors (TNF-α, IL-1β, MCP-1, and IL-8) in serum samples from rats with acute cerebral ischemic-reperfusion injury...
May 2015: Microvascular Research
Ying Sun, Dong Xi, Wen Ding, Faxi Wang, Haili Zhou, Qin Ning
PURPOSE: To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC). METHODS: Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry...
October 2014: Hepatology International
Jiemiao Hu, Jun Yan, Ganesh Rao, Khatri Latha, Willem W Overwijk, Amy B Heimberger, Shulin Li
Fibrinogen-like protein 2 (Fgl2), a member of the fibrinogen family, can be expressed as a membrane-associated protein with coagulation activity or in a secreted form possessing unique immune suppressive functions. The biological importance of Fgl2 is evident within viral-induced fibrin depositing inflammatory diseases and malignancies and provides a compelling rationale for Fgl2 expression to not only be considered as a disease biomarker but also as a therapeutic target. This article will provide a comprehensive review of the currently known biological properties of Fgl2 and clarifies future scientific directives...
September 26, 2014: International Reviews of Immunology
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