Linked Life Data

12393548

Source:http://linkedlifedata.com/resource/pubmed/id/12393548

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-1-16
pubmed:abstractText
Although dendritic cells (DCs) are the most potent antigen-presenting cells involved in numerous physiologic and pathologic processes, little is known about the signaling pathways that regulate DC activation and antigen-presenting function. Recently, we demonstrated that nuclear factor (NF)-kappaB activation is central to that process, as overexpression of IkappaBalpha blocks the allogeneic mixed lymphocyte reaction (MLR), an in vitro model of T-cell activation. In this study, we investigated the role of 2 putative NF-kappaB-inducing components, NF-kappaB-inducing kinase (NIK), and IkappaB kinase 2 (IKK2). Using an adenoviral gene transfer method to efficiently express dominant-negative (dn) forms of these molecules in monocyte-derived DCs, we found that IKK2dn but not NIKdn inhibited the allogeneic MLR. When DCs were fixed, this inhibitory effect of IKK2dn was lost, suggesting that IKK2 is involved in T-cell-derived signals that enhance DC antigen presentation during the allogeneic MLR period and does not have an effect on viability or differentiation state of DCs prior to coculture with T cells. One such signal is likely to be CD40 ligand (CD40L), as IKK2dn blocked CD40L but not lipopolysaccharide (LPS)-induced NF-kappaB activation, cytokine production, and up-regulation of costimulatory molecules and HLA-DR in DCs. In summary, our results demonstrate that IKK2 is essential for DC activation induced by CD40L or contact with allogeneic T cells, but not by LPS, whereas NIK is not required for any of these signals. In addition, our results support IKK2 as a potential therapeutic target for the down-regulation of unwanted immune responses that may occur during transplantation or autoimmunity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand, http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Chuk protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase, http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human, http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Ikbkb protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ikbke protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B kinase, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
983-91
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Ikappa B kinase 2 but not NF-kappa B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction.
pubmed:affiliation
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't