Linked Life Data

10706726

Source:http://linkedlifedata.com/resource/pubmed/id/10706726

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-3-28
pubmed:abstractText
Chemokines can promote interstitial fibrosis that is, in turn, a strong predictor of renal failure in chronic glomerulonephritides (GN). Resident renal cells, including renal tubular epithelial cells (RTEC), represent a prominent source of chemokine expression. Evaluating those factors responsible for sustained chemokine production by RTEC during GN is therefore crucial. The contribution of interstitial T cells to such expression, and in particular the precise nature of their interactions with RTEC, are poorly understood. Activated T cell/RTEC coculture induced production of high levels of monocyte chemoattractant protein-1 (MCP-1), RANTES, and IFN-inducible protein-10 from RTEC. Using double-chamber cultures and activated T cell plasma membrane preparations we demonstrated that both cell contact and soluble factors contributed to RTEC chemokine production. Importantly, different chemokines exhibited distinct activation requirements. Thus, for RANTES cell contact was essential, but not sufficient. In contrast, either soluble factors or cell contact induced MCP-1 and IFN-inducible protein-10 production, although both pathways were required for a maximal response. Neutralization experiments identified critical roles in this process for proinflammatory cytokines such as TNF-alpha, IL-1beta, and IFN-gamma as well as membrane molecules such as LFA-1, CD40 ligand, and membrane bound TNF-alpha. Finally, chemotactic bioassays of T cell/RTEC coculture supernatants demonstrated 80% reduction of monocyte migration following MCP-1 neutralization, indicating a dominant role for this chemokine. In summary, activation of renal tubular cells by infiltrating T cells can amplify and perpetuate local inflammatory responses through chemokine production differentially mediated by soluble and cell contact-dependent factors. Recognition of this regulatory diversity has important implications in the choice of potential therapeutic targets in GN.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3323-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10706726-Antigens, CD40, pubmed-meshheading:10706726-CD4-Positive T-Lymphocytes, pubmed-meshheading:10706726-CD40 Ligand, pubmed-meshheading:10706726-CD8-Positive T-Lymphocytes, pubmed-meshheading:10706726-Cell Communication, pubmed-meshheading:10706726-Cell Membrane, pubmed-meshheading:10706726-Cell Movement, pubmed-meshheading:10706726-Chemokine CCL2, pubmed-meshheading:10706726-Chemokines, pubmed-meshheading:10706726-Chronic Disease, pubmed-meshheading:10706726-Cytokines, pubmed-meshheading:10706726-Epithelial Cells, pubmed-meshheading:10706726-Glomerulonephritis, pubmed-meshheading:10706726-Humans, pubmed-meshheading:10706726-Kidney Tubules, pubmed-meshheading:10706726-Ligands, pubmed-meshheading:10706726-Lymphocyte Activation, pubmed-meshheading:10706726-Membrane Glycoproteins, pubmed-meshheading:10706726-Monocytes, pubmed-meshheading:10706726-Nephritis, Interstitial, pubmed-meshheading:10706726-Protein Binding, pubmed-meshheading:10706726-Solubility, pubmed-meshheading:10706726-T-Lymphocytes
pubmed:year
2000
pubmed:articleTitle
Distinct T cell/renal tubular epithelial cell interactions define differential chemokine production: implications for tubulointerstitial injury in chronic glomerulonephritides.
pubmed:affiliation
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. kuroiwat@arb.niams.nih.gov
pubmed:publicationType
Journal Article