| Intragraft TNF receptor signaling contributes to activation of innate and adaptive immunity in a renal allograft model. | |
| | |
MedLine Citation:
|
PMID: 19155971 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Increased levels of tumor necrosis factor (TNF) are a risk factor for allograft rejection. In vitro studies have shown that binding of TNF to its receptor activates signaling cascades that induce expression of many genes involved in inflammation. The role of intragraft TNF receptor (TNFR) signaling in activation of gene expression in allografts has not been studied. METHODS: Gene expression profiling and quantitative real-time polymerase chain reaction analysis were used to investigate the role of TNFR signaling in the early intragraft activation of cellular gene expression in renal allografts at 2 days posttransplant. RESULTS: The TNFRs play a critical role in activating intragraft expression of transcription factors controlling innate and adaptive immunity and stress responses (interferon regulatory factor [IRF]1, IRF 8, Isgf3g, and ATF3) of cytokines and receptors mediating inflammation (TNF, interleukin [IL]-6, interferon-gamma, oncostatin M receptor [OMCR], toll-like receptor [TLR]2, and IL-2Rgamma), of chemokines and adhesion molecules that recruit inflammatory cells (Cxcl9, Cxcl11, E-selectin, and intracellular adhesion molecule [ICAM]-1), of genes involved in costimulation of T cells and processing and presentation of antigens (H2-DMb, Psmb8, and CD40), and genes that mediate the response to interferons. In addition to its proinflammatory role, TNFR signaling induces expression of SOCS3, a negative regulator of IL-6 and OSMR signaling and Nfkbie, and a negative regulator of TNFR signal transduction. CONCLUSIONS: These studies illustrate the pleiotropic effect of TNF in both activation and down-modulation of the immune response and the complex interactions between the TNFRs and other cytokine signaling pathways in the early allograft response. |
| | |
Authors:
|
Mary Hummel; Sunil M Kurian; Simon Lin; Aleksey Borodyanskiy; Zheng Zhang; Zhigao Li; Soo Jung Kim; Daniel R Salomon; Michael Abecassis |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Transplantation Volume: 87 ISSN: 1534-6080 ISO Abbreviation: Transplantation Publication Date: 2009 Jan |
Date Detail:
|
Created Date: 2009-01-21 Completed Date: 2009-02-10 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0132144 Medline TA: Transplantation Country: United States |
Other Details:
|
Languages: eng Pagination: 178-88 Citation Subset: IM |
Affiliation:
|
Transplant Division, Department of Surgery, Northwestern University, Chicago, IL, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cytokines / genetics Gene Expression Profiling / methods Gene Expression Regulation Immunity, Innate* / genetics Inflammation / genetics, immunology* Kidney / immunology*, surgery* Kidney Transplantation / immunology* Male Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Models, Animal Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Receptors, Tumor Necrosis Factor / genetics, immunology* Reproducibility of Results Signal Transduction / genetics, immunology* Time Factors Transcription Factors / genetics Transplantation, Homologous Tumor Necrosis Factor-alpha / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
R01 AI042898/AI/NIAID NIH HHS; U19 AI063603/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cytokines; 0/Receptors, Tumor Necrosis Factor; 0/Transcription Factors; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Recovery of warm ischemic rat liver grafts by normothermic extracorporeal perfusion.
Next Document: Development of a humanized mouse model to study the role of macrophages in allograft injury.