Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in response to LPS or PMA stimulation

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Abstract
Increased expression of tissue factor (TF) procoagulant activity by blood monocytes and tissue macrophages is implicated in a number of thrombotic disorders, as well as in fibrin deposition associated with inflammatory lesions and immunological diseases. We found that interleukin 4 (IL-4), a T lymphocyte-derived cytokine known to regulate a number of monocyte functions, inhibited the production of TF by monocytes in response to endotoxin and phorbol myristate acetate (PMA) in vitro. IL-4 had a concentration-dependent inhibitory effect on functional TF procoagulant activity (PCA) and reduced the binding of an anti-TF antibody, as assessed by flow cytometry analysis. Moreover, IL-4 reduced LPS- and PMA-induced TF mRNA levels. TF mRNA stability was not modified by IL-4 after the arrest of transcription by actinomycin D. We thus conclude that mRNA suppression is mediated by an effect occurring at the transcriptional level. Our results also show that the suppressive effect of IL-4 is independent of an increase in the intracellular concentration of cyclic AMP, another established inhibitor of TF production. Locally produced IL-4 might thus contribute to limiting the consequences of monocyte activation.