Abstract:
:Imbalance in the production of cytokines and their inhibitors plays a part in inflammation in chronic destructive diseases. Direct cell-cell contact with stimulated T cells markedly induces the production of pro-inflammatory cytokines and matrix metalloproteinases in monocytes. This study demonstrates that direct contact with stimulated T cells favours the production of IL-1beta over that of IL-1 receptor antagonist (IL-1Ra) in both peripheral blood monocytes and the monocytic cell line THP-1. In contrast, soluble factors secreted by stimulated T cells favour the production of IL-1Ra. Differentiation of THP-1 cells with 1,25-(OH)2D3 did not affect the balance between IL-1beta and IL-1Ra production, enhancing both cytokines 2.3- and 1.6-fold, respectively. Among different inhibitors of phosphorylation and dephosphorylation processes, only okadaic acid, an inhibitor of serine/threonine phosphatases, differentially modulates the production of IL-1beta and IL-1Ra. Indeed, okadaic acid upregulated IL-1beta and decreased IL-1Ra at the mRNA and protein level in monocytic cells activated by membranes of stimulated T cells. These results suggest that serine/threonine phosphatases play a part in the differential regulation of the production of IL-1beta and IL-1Ra by monocytes upon direct cell-cell contact with stimulated T cells. This mechanism may regulate the balance between the pro-inflammatory cytokine and its inhibitor, which balance dictates in part the outcome of the inflammatory process.
journal_name
Cytokinejournal_title
Cytokineauthors
Vey E,Dayer JM,Burger Ddoi
10.1006/cyto.1997.0191subject
Has Abstractpub_date
1997-07-01 00:00:00pages
480-7issue
7eissn
1043-4666issn
1096-0023pii
S1043-4666(97)90191-5journal_volume
9pub_type
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