The Experts below are selected from a list of 87 Experts worldwide ranked by ideXlab platform
Chichao Chan - One of the best experts on this subject based on the ideXlab platform.
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experimental coronavirus retinopathy ecor retinal degeneration susceptible mice have an augmented interferon and Chemokine CXCL9 cxcl10 response early after virus infection
Journal of Neuroimmunology, 2008Co-Authors: Barbara Detrick, Maria Teresa Lee, M S Chin, L C Hooper, Chichao ChanAbstract:Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop the late phase. What host factors contribute to the distinct responses to the virus are unknown. Herein, we show that IFN-α, IFN-β and IFN-γ act in concert as part of the innate immune response to the retinal infection. At day 2, high serum levels of IFN-γ, CXCL9 and CXCL10, were detected in BALB/c mice. Moreover, elevated levels of CXCL9 and CXCL10 gene expression were detected in retinal tissue. Although IFN-γ and the Chemokines were detected in CD-1 mice, they were at significantly lower levels compared to BALB/c mice. These augmented innate responses observed correlated with the development of autoimmune reactivity and retinal degeneration and thus may contribute to the pathogenic processes.
Margaret H Chang - One of the best experts on this subject based on the ideXlab platform.
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adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis
Annals of the Rheumatic Diseases, 2020Co-Authors: Pui Y Lee, Grant S Schulert, Scott W Canna, Yuelong Huang, Jacob Sundel, Kacie J Hoyt, Rachel B Blaustein, Alexandra Wactor, Olha Halyabar, Margaret H ChangAbstract:Objective Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnosis and treatment. We evaluated adenosine deaminase 2 (ADA2), a protein of unknown function released principally by monocytes and macrophages, as a novel biomarker of MAS. Methods We established age-based normal ranges of peripheral blood ADA2 activity in 324 healthy children and adults. We compared these ranges with 173 children with inflammatory and immune-mediated diseases, including systemic and non-systemic JIA, Kawasaki disease, paediatric systemic lupus erythematosus and juvenile dermatomyositis. Results ADA2 elevation beyond the upper limit of normal in children was largely restricted to sJIA with concomitant MAS, a finding confirmed in a validation cohort of sJIA patients with inactive disease, active sJIA without MAS or sJIA with MAS. ADA2 activity strongly correlated with MAS biomarkers including ferritin, interleukin (IL)-18 and the interferon (IFN)-γ-inducible Chemokine CXCL9 but displayed minimal association with the inflammatory markers C reactive protein and erythrocyte sedimentation rate. Correspondingly, ADA2 paralleled disease activity based on serial measurements in patients with recurrent MAS episodes. IL-18 and IFN-γ elicited ADA2 production by peripheral blood mononuclear cells, and ADA2 was abundant in MAS haemophagocytes. Conclusions These findings collectively identify the utility of plasma ADA2 activity as a biomarker of MAS and lend further support to a pivotal role of macrophage activation in this condition.
Barbara Detrick - One of the best experts on this subject based on the ideXlab platform.
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experimental coronavirus retinopathy ecor retinal degeneration susceptible mice have an augmented interferon and Chemokine CXCL9 cxcl10 response early after virus infection
Journal of Neuroimmunology, 2008Co-Authors: Barbara Detrick, Maria Teresa Lee, M S Chin, L C Hooper, Chichao ChanAbstract:Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop the late phase. What host factors contribute to the distinct responses to the virus are unknown. Herein, we show that IFN-α, IFN-β and IFN-γ act in concert as part of the innate immune response to the retinal infection. At day 2, high serum levels of IFN-γ, CXCL9 and CXCL10, were detected in BALB/c mice. Moreover, elevated levels of CXCL9 and CXCL10 gene expression were detected in retinal tissue. Although IFN-γ and the Chemokines were detected in CD-1 mice, they were at significantly lower levels compared to BALB/c mice. These augmented innate responses observed correlated with the development of autoimmune reactivity and retinal degeneration and thus may contribute to the pathogenic processes.
Pui Y Lee - One of the best experts on this subject based on the ideXlab platform.
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adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis
Annals of the Rheumatic Diseases, 2020Co-Authors: Pui Y Lee, Grant S Schulert, Scott W Canna, Yuelong Huang, Jacob Sundel, Kacie J Hoyt, Rachel B Blaustein, Alexandra Wactor, Olha Halyabar, Margaret H ChangAbstract:Objective Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnosis and treatment. We evaluated adenosine deaminase 2 (ADA2), a protein of unknown function released principally by monocytes and macrophages, as a novel biomarker of MAS. Methods We established age-based normal ranges of peripheral blood ADA2 activity in 324 healthy children and adults. We compared these ranges with 173 children with inflammatory and immune-mediated diseases, including systemic and non-systemic JIA, Kawasaki disease, paediatric systemic lupus erythematosus and juvenile dermatomyositis. Results ADA2 elevation beyond the upper limit of normal in children was largely restricted to sJIA with concomitant MAS, a finding confirmed in a validation cohort of sJIA patients with inactive disease, active sJIA without MAS or sJIA with MAS. ADA2 activity strongly correlated with MAS biomarkers including ferritin, interleukin (IL)-18 and the interferon (IFN)-γ-inducible Chemokine CXCL9 but displayed minimal association with the inflammatory markers C reactive protein and erythrocyte sedimentation rate. Correspondingly, ADA2 paralleled disease activity based on serial measurements in patients with recurrent MAS episodes. IL-18 and IFN-γ elicited ADA2 production by peripheral blood mononuclear cells, and ADA2 was abundant in MAS haemophagocytes. Conclusions These findings collectively identify the utility of plasma ADA2 activity as a biomarker of MAS and lend further support to a pivotal role of macrophage activation in this condition.
M L Berres - One of the best experts on this subject based on the ideXlab platform.
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Chemokine CXCL9 attenuates liver fibrosis associated angiogenesis in mice
Hepatology, 2012Co-Authors: Hacer Sahin, Erawan Borkhamkamphorst, Christoph Kuppe, Mirko Moreno Zaldivar, Christoph Grouls, M Alsamman, A Nellen, P Schmitz, D Heinrichs, M L BerresAbstract:Recent data suggest that the Chemokine receptor CXCR3 is functionally involved in fibroproliferative disorders, including liver fibrosis. Neoangiogenesis is an important pathophysiological feature of liver scarring, but a functional role of angiostatic CXCR3 Chemokines in this process is unclear. We therefore investigated neoangiogenesis in carbon tetrachloride (CCl4)-induced liver fibrosis in Cxcr3−/− and wildtype mice by histological, molecular, and functional imaging methods. Furthermore, we assessed the direct role of vascular endothelial growth factor (VEGF) overexpression on liver angiogenesis and the fibroproliferative response using a Tet-inducible bitransgenic mouse model. The feasibility of attenuation of angiogenesis and associated liver fibrosis by therapeutic treatment with the angiostatic Chemokine CXCL9 was systematically analyzed in vitro and in vivo. The results demonstrate that fibrosis progression in Cxcr3−/− mice was strongly linked to enhanced neoangiogenesis and VEGF/VEGFR2 expression compared with wildtype littermates. Systemic VEGF overexpression led to a fibrogenic response within the liver and was associated with a significantly increased CXCL9 expression. In vitro, CXCL9 displayed strong antiproliferative and antimigratory effects on VEGF-stimulated endothelial cells and stellate cells by way of reduced VEGFR2 (KDR), phospholipase Cγ (PLCγ), and extracellular signal-regulated kinase (ERK) phosphorylation, identifying this Chemokine as a direct counter-regulatory molecule of VEGF signaling within the liver. Accordingly, systemic administration of CXCL9 led to a strong attenuation of neoangiogenesis and experimental liver fibrosis in vivo. Conclusion: The results identify direct angiostatic and antifibrotic effects of the Cxcr3 ligand CXCL9 in a model of experimental liver fibrosis. The amelioration of liver damage by systemic application of CXCL9 might offer a novel therapeutic approach for chronic liver diseases associated with increased neoangiogenesis. (HEPATOLOGY 2012)
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antifibrotic effects of CXCL9 and its receptor cxcr3 in livers of mice and humans
Gastroenterology, 2009Co-Authors: H E Wasmuth, Mirko Moreno Zaldivar, M L Berres, F Lammert, Ralf Weiskirchen, C Hellerbrand, D Scholten, Henning W Zimmermann, Konrad L Streetz, Frank TackeAbstract:Background & Aims Fibrosis is the hallmark of chronic liver diseases, yet many aspects of its mechanism remain to be defined. Chemokines are ubiquitous chemotactic molecules that mediate many acute and chronic inflammatory conditions, and CXC Chemokine genes colocalize with a locus previously shown to include fibrogenic genes. We investigated the roles of the Chemokine CXCL9 and its receptor CXCR3 in liver fibrosis. Methods The effects of CXCL variants on fibrogenesis were analyzed using samples from patients with hepatitis C virus infection and by induction of fibrosis in CXCR3 −/− and wild-type mice. In mice, intrahepatic immune cell subsets were investigated and interferon gamma messenger RNA levels were measured at baseline and after injury. Human serum CXCL9 levels were measured and correlated with CXCL9 variant and fibrosis severity. The effects of stimulation with CXCL9 were investigated on human hepatic stellate cells (LX-2). Results Specific CXCL9 variants were associated with liver fibrosis in mice and humans; CXCL9 serum concentrations correlated with genotypes and levels of fibrosis in patients. In contrast to other Chemokines, CXCL9 exerted antifibrotic effects in vitro, suppressing collagen production in LX-2 cells. CXCR3 −/− mice had increased liver fibrosis; progression was associated with decreased numbers of intrahepatic interferon gamma–positive T cells and reduced interferon gamma messenger RNA, indicating that CXCL9-CXCR3 regulates Th1-associated immune pathways. Conclusions This is the first description of a Chemokine-based antifibrotic pathway in the liver; antifibrotic therapies might be developed to modulate CXC Chemokine levels.