Results 1 -
3 of
3
IL-4–Stat6 Signaling Induces Tristetraprolin Expression and Inhibits TNF- � Production in Mast Cells
"... Increasing evidence has revealed that mast cell–derived tumor necrosis factor � (TNF-�) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF- � production in mast cells. IL ..."
Abstract
-
Cited by 4 (0 self)
- Add to MetaCart
(Show Context)
Increasing evidence has revealed that mast cell–derived tumor necrosis factor � (TNF-�) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF- � production in mast cells. IL-4 inhibited immunoglobulin E–induced TNF- � production and neutrophil recruitment in the peritoneal cavity in wild-type mice but not in signal transducers and activators of transcription 6 (Stat6)–deficient mice. IL-4 also inhibited TNF- � production in cultured mast cells by a Stat6-dependent mechanism. IL-4–Stat6 signaling induced TNF- � mRNA destabilization in an AU-rich element (ARE)–dependent manner, but did not affect TNF-� promoter activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by a Stat6-dependent mechanism, and the depletion of TTP expression by RNA interference prevented IL-4–induced down-regulation of TNF- � production in mast cells. These results suggest that IL-4–Stat6 signaling induces TTP expression and, thus, destabilizes TNF-� mRNA in an ARE-dependent manner. Key words: mast cell–derived TNF- � • mRNA destabilization • RNA interference • AU-rich element • IgE
Study of plasma protein C and inflammatory pathways: Biomarkers for dimethylnitrosamine-induced liver fibrosis in rats
"... Abstract The present investigation was designed to identify potential biomarker(s) and assess the involvement of inflammatory pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Following DMN-treatment (10 mg/ml/kg, i.p., given three consecutive days each week for 4 weeks) body and ..."
Abstract
- Add to MetaCart
(Show Context)
Abstract The present investigation was designed to identify potential biomarker(s) and assess the involvement of inflammatory pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Following DMN-treatment (10 mg/ml/kg, i.p., given three consecutive days each week for 4 weeks) body and liver weights were significantly decreased concurrent with increasing severity of liver damage assessed by bridging fibrosis, a histopathologic assessment and characteristic of human liver disease. Protein C along with albumin, C-reactive-protein (CRP), haptoglobin and total protein were significantly reduced and correlated with changes in liver histopathology. Biochemical markers of liver functions were significantly increased and correlated with changes in liver histopathology and plasma levels of protein C. Soluble intracellular-adhesion-molecule -1 (sICAM-1) levels were increased significantly but were poorly correlated with histopathology and protein C levels. Inflammatory chemokines and other analytes, monocyte-chemoattractant-protein-1 and 3 (MCP-1 and MCP-3), macrophage-colony-stimulating-factor (M-CSF) were significantly increased during the disease progression, whereas macrophage-derived-chemokine (MDC) and CRP were significantly suppressed. Circulating neutrophils and monocytes were also increased along with disease progression. The differential changes in sICAM-1, hyaluronic acid, gammaglutamyltranspeptidase (GGT), neutrophil and other inflammatory chemokines suggest the involvement of inflammatory pathways in DMNinduced liver fibrosis. In conclusion, the progressive changes in protein C along with other noninvasive biochemical parameters whose levels were significantly correlated with disease progression may serve as biomarkers for pharmacological assessment of targeted therapy for liver fibrosis.
Original article Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis
, 2002
"... The mannose-binding lectin (MBL) (also known as the mannose-binding protein) is a serum protein that plays a role as an “ante-antibody ” in innate immunity. In man, MBL is encoded by a single gene, whereas in mice there are two homologous proteins, MBL-A and MBL-C. In order to evaluate the relative ..."
Abstract
- Add to MetaCart
(Show Context)
The mannose-binding lectin (MBL) (also known as the mannose-binding protein) is a serum protein that plays a role as an “ante-antibody ” in innate immunity. In man, MBL is encoded by a single gene, whereas in mice there are two homologous proteins, MBL-A and MBL-C. In order to evaluate the relative roles of these two forms of MBL, we created MBL-A null mice that were MBL-C sufficient. We found MBL-A null mice had enhanced survival in a septic peritonitis model compared to wild-type mice and complement 3 null mice at 24 h, 48 h and 10 d (P < 0.05). Reconstitution of these mice with human MBL reversed the phenotype. Surviving mice had significantly decreased TNF-α and IL-6 levels in the blood and peritoneal cavity (P < 0.01). In vitro studies indicate that bacteria opsonized with MBL-A-deficient serum induced significantly less cytokine by peritoneal macrophages compared to those with wild-type serum. Our results indicate that MBL-A is a modulator of inflammation in vivo and in vitro in the mouse and that the role of MBL may extend beyond its role as an opsonin. © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved.
