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Start Over Author "Fayad R" Topic apoptosis
3 results on '"Fayad R"'

1. Apoptosis resistance in ulcerative colitis: high expression of decoy receptors by lamina propria T cells.

Author

Fayad R, Brand MI, Stone D, Keshavarzian A, and Qiao L

Subjects
Adult, Apoptosis Regulatory Proteins antagonists & inhibitors, Apoptosis Regulatory Proteins metabolism, Cells, Cultured, Fas Ligand Protein, Female, GPI-Linked Proteins, Health, Humans, Intestinal Mucosa cytology, Male, Membrane Glycoproteins antagonists & inhibitors, Membrane Glycoproteins metabolism, Middle Aged, Receptors, Antigen, T-Cell immunology, Receptors, Tumor Necrosis Factor immunology, Receptors, Tumor Necrosis Factor, Member 10c, T-Lymphocytes immunology, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor Decoy Receptors, Tumor Necrosis Factor Inhibitors, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factors metabolism, Apoptosis, Colitis, Ulcerative metabolism, Colitis, Ulcerative pathology, Intestinal Mucosa immunology, Receptors, Tumor Necrosis Factor metabolism, T-Lymphocytes cytology, T-Lymphocytes metabolism
Abstract

Intestinal mucosa is constantly exposed to normal environmental antigens. A significant number of intestinal mucosal T cells are being deleted through apoptosis. In contrast, T cells from inflamed mucosa of ulcerative colitis patients did not undergo apoptosis. In this study, we determined whether the apoptosis of normal mucosal T cells was induced by antigen receptor stimulation and further determined pathways that mediated the apoptosis. Freshly isolated lamina propria T cells were stimulated with CD3 mAb and apoptosis was determined by Annexin V staining. Normal mucosal T cells underwent apoptosis upon CD3 mAb stimulation whereas the T cells from inflamed mucosa did not. The apoptosis in normal T cells was blocked by TRAIL-R1:Fc and an inhibiting CD95 antibody. Interestingly, decoy receptor (DcR)1, DcR2, and DcR3 that compete with death receptor (DR)4/5 and CD95 were highly expressed by the T cells from inflamed mucosa, but much lower by T cells from normal mucosa. Our data suggest that normal mucosal T cells are constantly deleted in response to environmental antigens mediated through DR4/5 and CD95 pathways and mucosal T cells from ulcerative colitis resist to undergoing apoptosis due to highly expression of DcR1, DcR2, and DcR3.

Published
2006
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2. Induction of thymocyte apoptosis by systemic administration of concanavalin A in mice: role of TNF-alpha, IFN-gamma and glucocorticoids.

Author

Fayad R, Sennello JA, Kim SH, Pini M, Dinarello CA, and Fantuzzi G

Subjects
Animals, CD4 Antigens immunology, CD8 Antigens immunology, Concanavalin A toxicity, Female, Interferon-gamma antagonists & inhibitors, Liver drug effects, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Spleen cytology, Spleen drug effects, Spleen immunology, Thymus Gland immunology, Thymus Gland metabolism, Tumor Necrosis Factor-alpha antagonists & inhibitors, Apoptosis drug effects, Apoptosis immunology, Concanavalin A pharmacology, Glucocorticoids physiology, Interferon-gamma physiology, Thymus Gland cytology, Thymus Gland drug effects, Tumor Necrosis Factor-alpha physiology
Abstract

Administration of concanavalin A (Con A) is a well-established model of acute immune-mediated hepatitis. Here, we demonstrate that intravenous injection of Con A in mice induces profound thymic atrophy. Compared to liver damage, the kinetics of Con A-induced thymic atrophy is slower and more prolonged; the nadir in thymocyte number is reached 4 days after Con A injection, whereas peak transaminase levels are observed at 12-24 h. Marked alterations in the ratio of CD4+ and CD8+cells in the thymus and spleen and significantly increased rates of thymocyte and splenocyte apoptosis are observed. Neutralization of the cytokines TNF-alpha or IFN-gamma, which protects mice from Con A-induced hepatitis, prevents thymic atrophy as well as alterations in CD4+ and CD8+ cell numbers and apoptosis rates. However, neither TNF-alpha nor IFN-gamma are detectable in thymocyte lysates after Con A injection, whereas both cytokines are present in liver, spleen and serum. Administration of the glucocorticoid receptor antagonist mifepristone does not prevent thymic atrophy, thus ruling out a possible contribution of endogenous glucocorticoids. Con A-induced thymic atrophy is accompanied by down-regulation of Bcl-2 expression in the thymus, which is prevented by neutralization of TNF-alpha or IFN-gamma. These data demonstrate that the thymus is a critical target organ of Con A-induced inflammation; the effects of Con A on the thymus are mediated by extrathymic production of TNF-alpha and IFN-gamma, but not by glucocorticoids.

Published
2005
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3. Regulation of T cell-mediated hepatic inflammation by adiponectin and leptin

Author

Robert H. Eckel, Alison M. Morris, Jeffrey M. Friedman, Charles A. Dinarello, Raja Fayad, Jason M. Montez, Giamila Fantuzzi, Esra Asilmaz, Joseph A. Sennello, Coates, Alison Mary, Sennello, J, Fayad, R, Eckel, R, Asilmaz, E, Montez, J, Friedman, J, Dinarello, C, and Fantuzzi, G

Subjects
Leptin, medicine.medical_specialty, Lipodystrophy, T-Lymphocytes, medicine.medical_treatment, T cell, Mice, Obese, Adipose tissue, Adipokine, Apoptosis, Mice, Transgenic, Biology, Lymphocyte Activation, Autoimmune Diseases, Hepatitis, Mice, Endocrinology, Internal medicine, Concanavalin A, In Situ Nick-End Labeling, medicine, Animals, Obesity, Leptin Deficiency, Adiponectin, Tumor Necrosis Factor-alpha, Natural killer T cell, DNA-Binding Proteins, Killer Cells, Natural, Cytokine, medicine.anatomical_structure, CCAAT-Enhancer-Binding Proteins, Cytokines, Intercellular Signaling Peptides and Proteins, Sterol Regulatory Element Binding Protein 1, hormones, hormone substitutes, and hormone antagonists, Transcription Factors
Abstract

Concanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNFα protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNFα was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNFα-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNFα-induced death.

Published
2005

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