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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Suppl
pubmed:dateCreated
2009-9-10
pubmed:abstractText
Interleukin-27 (IL-27) is a new IL-12-related heterodimeric cytokine comprising a novel p28 molecule and the Epstein-Barr-virus-induced gene 3 (EBI3) molecules. It augments initiation of T helper type 1-mediated immunity by enhancing the proliferation and cytokine production of T cells. In this study, we examined whether a secreted form of IL-27 subunits would inhibit IL-27-mediated immunological responses. COS-7 cells transduced with the mouse (m) p28 gene secreted a monomeric mp28 protein; however, those transduced with the mEBI3 gene did not detect a mEBI3 protein in the culture supernatants. The secreted mp28 prevented the IL-27-mediated signal transduction and activator of transcription 1 phosphorylation and subsequently inhibited the IL-27-mediated intercellular adhesion molecule-1 induction and interferon-gamma production in CD4(+) T cells. We generated mp28-expressing murine carcinoma Colon 26 cells and inoculated a mixture of the mp28- and mIL-27-expressing Colon 26 cells into syngeneic BALB/c mice. Simultaneous production of mp28 and mIL-27 from Colon 26 cells suppressed IL-27-mediated anti-tumour effects in the mice. We examined the p28-mediated immune suppression by inoculating mp28-expressing myoblasts into allogeneic mice. Forced production of mp28 suppressed the allogeneic cytotoxic T-lymphocyte induction and subsequently retarded the graft rejection. Furthermore, production of both mp28 and mp40, which inhibits the functions of IL-12 and IL-23, prolonged the graft survival longer than the grafts expressing either mp28 or mp40. We propose that p28 can be a regulatory subunit for IL-27-mediated cellular immune responses and a possible therapeutic agent to suppress unfavourable immune responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1365-2567
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e816-25
pubmed:dateRevised
2010-9-2
pubmed:meshHeading
pubmed-meshheading:19740343-Animals, pubmed-meshheading:19740343-CD4-Positive T-Lymphocytes, pubmed-meshheading:19740343-COS Cells, pubmed-meshheading:19740343-Cell Adhesion Molecules, pubmed-meshheading:19740343-Cell Line, Tumor, pubmed-meshheading:19740343-Cercopithecus aethiops, pubmed-meshheading:19740343-Female, pubmed-meshheading:19740343-Graft Survival, pubmed-meshheading:19740343-Interferon-gamma, pubmed-meshheading:19740343-Interleukin-17, pubmed-meshheading:19740343-Mice, pubmed-meshheading:19740343-Mice, Inbred BALB C, pubmed-meshheading:19740343-Mice, Inbred C57BL, pubmed-meshheading:19740343-Myoblasts, pubmed-meshheading:19740343-Neoplasms, pubmed-meshheading:19740343-Phosphorylation, pubmed-meshheading:19740343-Protein Subunits, pubmed-meshheading:19740343-Receptors, Cytokine, pubmed-meshheading:19740343-Receptors, Interleukin-12, pubmed-meshheading:19740343-STAT1 Transcription Factor, pubmed-meshheading:19740343-T-Lymphocytes, Cytotoxic, pubmed-meshheading:19740343-Th1 Cells, pubmed-meshheading:19740343-Transduction, Genetic
pubmed:year
2009
pubmed:articleTitle
The secreted form of p28 subunit of interleukin (IL)-27 inhibits biological functions of IL-27 and suppresses anti-allogeneic immune responses.
pubmed:affiliation
Division of Pathology, Chiba Cancer Centre Research Institute, Nitona, Chiba, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't