Linked Life Data

17928893

Source:http://linkedlifedata.com/resource/pubmed/id/17928893

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-12
pubmed:abstractText
Therapeutic antibodies against tumor necrosis factor (TNF) (infliximab) and IFNgamma (fontolizumab) have been developed to treat autoimmune diseases. While the primary targets of these antibodies are clearly defined, the set of inflammatory molecules, which is altered by use of these inhibitors, is poorly understood. We elucidate the target genes of these antibodies in activated human peripheral blood mononuclear cells from healthy volunteers. While genes suppressed by fontolizumab overlap with known IFNgamma-induced genes, majority of genes suppressed by infliximab have previously not been traced to TNF signaling. With this approach we were able to extrapolate new TNF-associated genes to be upregulated in psoriasis vulgaris, an "autoimmune" disease effectively treated with TNF antagonists. These genes represent potential therapeutic targets of TNF antagonists in psoriasis. Furthermore, these data establish an unexpected effect of TNF blockade on IFNgamma synthesis by T cells. Synthesis of IFNgamma, a cytokine of Th1-polarized T cells, is suppressed by 8.1-fold (P<0.01) at the mRNA level, while synthesis of IFNgamma is eliminated in >60% of individual T cells. These data suggest that TNF blockade with infliximab can suppress a major pathway of the adaptive immune response and this observation provides a key rationale for targeting TNF in "Type-1" T-cell-mediated autoimmune diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
655-66
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Insights into gene modulation by therapeutic TNF and IFNgamma antibodies: TNF regulates IFNgamma production by T cells and TNF-regulated genes linked to psoriasis transcriptome.
pubmed:affiliation
Department of Investigative Dermatology, Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural