Linked Life Data

20639459

Source:http://linkedlifedata.com/resource/pubmed/id/20639459

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-2
pubmed:abstractText
We reported that inhibiting matrix metalloproteinases (MMP), known to remodel the extracellular matrix, also down-regulated antigen-specific T-cell responses. However, the direct role of MMP2 and MMP9 in regulating intracellular function in T cells is unknown. Markers of cellular activation and cytokine profiles were examined in anti-CD3-stimulated wild-type C57BL/6 mouse-derived CD4(+) or CD8(+) T cells, or MMP2- or MMP9-deficient (-/-) mice. MMP-sufficient T cells were also treated with SB-3CT, a highly selective inhibitor of MMP2 and MMP9. The effect of MMP-specific inhibition on T cell-dependent, antigen-specific murine lung injury was examined in vivo. SB-3CT induced dose-dependent reductions in anti-CD3-stimulated T-cell proliferation. Although MMP2(-/-) cells were reduced 20%, anti-CD3-induced proliferation was down-regulated 80-85% in MMP9(-/-) or in SB-3CT-treated wild-type CD4(+) and CD8(+) T cells. Intracellular calcium flux was augmented in response to MMP inhibition or deficiency in the same cells, and IL-2 production was reduced in CD4(+) and CD8(+) MMP9(-/-) T cells. SB-3CT-mediated MMP2 and MMP9 inhibition abrogated antigen-specific CD8(+) T cell-mediated lung injury in vivo. MMPs, particularly MMP9, may function intracellularly to regulate T-cell activation. T cell-targeted MMP inhibition may provide a novel approach of immune regulation in the treatment of T cell-mediated diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1535-4989
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
700-8
pubmed:meshHeading
pubmed-meshheading:20639459-Animals, pubmed-meshheading:20639459-Antigens, Thy-1, pubmed-meshheading:20639459-CD4-Positive T-Lymphocytes, pubmed-meshheading:20639459-CD8-Positive T-Lymphocytes, pubmed-meshheading:20639459-Calcium, pubmed-meshheading:20639459-Extracellular Matrix, pubmed-meshheading:20639459-Female, pubmed-meshheading:20639459-Gene Expression Regulation, Enzymologic, pubmed-meshheading:20639459-Immunosuppressive Agents, pubmed-meshheading:20639459-Lung, pubmed-meshheading:20639459-Matrix Metalloproteinase 2, pubmed-meshheading:20639459-Matrix Metalloproteinase 9, pubmed-meshheading:20639459-Mice, pubmed-meshheading:20639459-Mice, Inbred BALB C, pubmed-meshheading:20639459-Mice, Inbred C57BL, pubmed-meshheading:20639459-Mice, Transgenic, pubmed-meshheading:20639459-Models, Biological
pubmed:year
2011
pubmed:articleTitle
Endogenous matrix metalloproteinases 2 and 9 regulate activation of CD4+ and CD8+ T cells.
pubmed:affiliation
Department of Biochemistry, Indiana University School of Medicine, Indianapolis, 46202, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural