scholarly journals Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK/TGF-β1 signaling pathway

2021 ◽  
Author(s):  
Qing-shan Liang ◽  
Jian-Gang Xie ◽  
ChaoPing Yu ◽  
ZhuSheng Feng ◽  
JingChang Ma ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Liver Fibrosis ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Jnk Signaling ◽  
Hepatic Macrophages ◽  
Tumor Necrosis Factor Superfamily ◽  
Tgf Β1 ◽  
Necrosis Factor

AbstractSplenectomy has been reported to improve liver fibrosis in patients with cirrhosis and hypersplenism. However, the mechanisms remain unclear. Tumor necrosis factor superfamily 14 (TNFSF14; also known as LIGHT) is highly expressed in the context of fibrosis and promotes disease progression in patients with fibrotic diseases such as pulmonary and skin fibrosis. Here, we determined whether splenectomy controls the production of LIGHT to improve liver fibrosis. Splenectomy reduced serum LIGHT levels in cirrhotic patients with hypersplenism and a ConA-induced liver fibrosis mouse model. Blocking LIGHT resulted in the downregulation of TGF-β1 in RAW264.7 cells. LIGHT treatment of RAW264.7 and JS1 cells in coculture regulated transforming growth factor-β1 (TGF-β1) expression through the activation of JNK signaling. Small interfering RNA-mediated silencing of lymphotoxin β receptor (LTβR) in macrophages resulted in pronounced decreases in the levels of fibrosis and αSMA in JS1 cells. These results indicated that LIGHT bound to LTβR and drove liver fibrosis in vitro. Blocking TGF-β1 abolished the effect of LIGHT in vitro. Furthermore, the administration of recombinant murine LIGHT protein-induced liver fibrosis with splenectomy, while blocking LIGHT without splenectomy improved liver fibrosis in vivo, revealing that the decrease in fibrosis following splenectomy was directly related to reduced levels of LIGHT. Thus, high levels of LIGHT derived from the spleen and hepatic macrophages activate JNK signaling and lead to increased TGF-β1 production in hepatic macrophages. Splenectomy attenuates liver fibrosis by decreasing the expression of LIGHT.

scholarly journals Toxoplasma gondii Infection of Neurons Induces Neuronal Cytokine and Chemokine Production, but Gamma Interferon- and Tumor Necrosis Factor-Stimulated Neurons Fail To Inhibit the Invasion and Growth of T. gondii

2001 ◽  
Vol 69 (12) ◽  
pp. 7889-7893 ◽  
Author(s):  
D. Schlüter ◽  
M. Deckert ◽  
H. Hof ◽  
K. Frei
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Gamma Interferon ◽  
Chemokine Production ◽  
Ifn Γ ◽  
Tgf Β1 ◽  
Necrosis Factor

ABSTRACT The intracellular parasite Toxoplasma gondii has the capacity to persist in the brain within neurons. In this study we demonstrated that T. gondiiinfected murine cerebellar neurons in vitro and replicated within these cells. Stimulation with gamma interferon (IFN-γ) and/or tumor necrosis factor (TNF) did not enable neurons to inhibit parasite invasion and replication. Cultured neurons constitutively produced interleukin 1 (IL-1), IL-6, macrophage inflammatory protein 1α (MIP-1α), and MIP-1β but not transforming growth factor β1 (TGF-β1), IL-10, and granulocyte-macrophage colony-stimulating factor. Neuronal expression of some cytokines (IL-6, TGF-β1) and chemokines (MIP-1β) was regulated by infection and/or by IFN-γ and TNF.

Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4107-4114 ◽  
Author(s):  
Lorenzo Cosmi ◽  
Francesco Liotta ◽  
Elena Lazzeri ◽  
Michela Francalanci ◽  
Roberta Angeli ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Functional Features ◽  
Tgf Β1 ◽  
Necrosis Factor

Abstract CD8+CD25+ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8+CD25+ thymocytes did not produce cytokines, but most of them expressed surface CTLA-4 and transforming growth factor β1 (TGF-β1). Like CD4+CD25+, CD8+CD25+ thymocytes suppressed the proliferation of autologous CD25-T cells via a contact-dependent mechanism. The suppressive activity of CD8+CD25+ thymocytes was abrogated by a mixture of anti-CTLA-4 and anti-TGF-β1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor α chain on target T cells. These results demonstrate the existence of a subset of human CD8+CD25+ thymocytes sharing phenotype, functional features, and mechanism of action with CD4+CD25+ T regulatory cells. (Blood. 2003;102:4107-4114)

Modulation of Pro- and Antifibrinolytic Properties of Human Peritoneal Mesothelial Cells by Transforming Growth Factor β1 (TGF- β1), Tumor Necrosis Factor α (TNF-α) and Interleukin β1 (IL-1β)

1998 ◽  
Vol 79 (02) ◽  
pp. 362-370 ◽  
Author(s):  
Anne Elbrecht ◽  
Carsten Schauerte ◽  
Bernd Klosterhalfen ◽  
Baffour Amo-Takyi ◽  
Johanna Gehlen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Plasminogen Activator ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Mesothelial Cells ◽  
Tnf Α ◽  
Tgf Β1 ◽  
Necrosis Factor ◽  
Pai 1

SummaryA decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF- β1) and interleukin 1β (IL-1β) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-β1, TNF-α and IL-1β induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.

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