Direct contact with stimulated T cells induces the expression of IL-1beta and IL-1 receptor antagonist in human monocytes. Involvement of serine/threonine phosphatases in differential regulation.
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.
Vey
E
E
Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Dayer
J M
JM
Burger
D
D
D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D010749:Phosphoprotein Phosphatases