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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2009-9-25
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pubmed:abstractText |
T cell development in the thymus is controlled by thymic epithelial cells (TE). While it is accepted that TE interact with maturing T cells, the mechanisms by which they trigger 'death by neglect' of double-positive (DP) thymocytes are poorly understood. We and others have demonstrated a role for TE-derived glucocorticoids (GCs) in this process. We have studied TE-induced apoptosis using an in vitro system based on co-culturing a thymic epithelial cell line (TEC) with DP thymic lymphoma cells or thymocytes (DP thymic cells). Here, we demonstrate that nitric oxide (NO*) is also involved in this death process. The inducible nitric oxide synthase (iNOS) inhibitors N(G)-methyl-L-arginine and 1,4-PBIT attenuated TEC-induced apoptosis of DP thymic cells. Co-cultivation of TEC with DP thymic cells increased the expression of iNOS in TEC. A concomitant increase in NO* was detected by staining with DAF-FM diacetate. Moreover, the iNOS-regulating cytokines IL-1alpha, IL-1beta and IFNgamma were up-regulated upon interaction of TEC with DP thymic cells. Neutralizing IL-1R or IFNgamma reduced TEC-induced apoptosis of DP thymic cells. Cardinally, NO* synergizes with GCs in eliciting apoptosis of DP thymic cells. Our data indicate that a cross-talk between DP thymic cells and TEC is required for proper induction of iNOS-up-regulating cytokines with a subsequent increase in iNOS expression and NO* production in TEC. NO*, in turn, cooperates with GCs in promoting death by neglect. We suggest that NO* together with GCs fine-tune the T cell selection process.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/Mifepristone,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/S,S'-1,4-phenylene-bis(1,2-ethanediy...,
http://linkedlifedata.com/resource/pubmed/chemical/Thiourea,
http://linkedlifedata.com/resource/pubmed/chemical/omega-N-Methylarginine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1460-2377
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1113-23
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pubmed:meshHeading |
pubmed-meshheading:19692538-Animals,
pubmed-meshheading:19692538-Apoptosis,
pubmed-meshheading:19692538-Coculture Techniques,
pubmed-meshheading:19692538-Enzyme Inhibitors,
pubmed-meshheading:19692538-Epithelial Cells,
pubmed-meshheading:19692538-Glucocorticoids,
pubmed-meshheading:19692538-Hormone Antagonists,
pubmed-meshheading:19692538-Interferon-gamma,
pubmed-meshheading:19692538-Interleukin-1alpha,
pubmed-meshheading:19692538-Interleukin-1beta,
pubmed-meshheading:19692538-Mice,
pubmed-meshheading:19692538-Mice, Inbred BALB C,
pubmed-meshheading:19692538-Mice, Inbred C57BL,
pubmed-meshheading:19692538-Mifepristone,
pubmed-meshheading:19692538-Nitric Oxide,
pubmed-meshheading:19692538-Nitric Oxide Synthase Type II,
pubmed-meshheading:19692538-Receptors, Glucocorticoid,
pubmed-meshheading:19692538-Thiourea,
pubmed-meshheading:19692538-Thymus Gland,
pubmed-meshheading:19692538-Up-Regulation,
pubmed-meshheading:19692538-omega-N-Methylarginine
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pubmed:year |
2009
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pubmed:articleTitle |
Nitric oxide cooperates with glucocorticoids in thymic epithelial cell-mediated apoptosis of double positive thymocytes.
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pubmed:affiliation |
Department of Immunology, The Lautenberg Center for General and Tumor Immunology, Institute of Medical Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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