Thrombin-induced interleukin-8 production and its regulation by interferon-γ and prostaglandin E₂ in human monocytic U937 cells

Blood coagulation and inflammation pathways are linked in many aspects. A number of serum factors involved in coagulation cascades affect directly or indirectly inflammatory responses, whereas proinflammatory cytokines influence blood coagulation pathways. In this work we demonstrated that thrombin is an effective stimulus in inducing interleukin (IL)-8 expression in human monocytic cell line U937. IL-8 induction was found at the mRNA and protein levels. The effect of thrombin on IL-8 production was mimicked by thrombin receptor-activating peptide indicating that thrombin effect was mediated by the specific receptor for thrombin. Moreover, thrombin-induced IL-8 production by U937 cells was differentially regulated by interferon (IFN)-γ and prostaglandin (PG)E₂. While IFN-γ enhanced thrombin-induced IL-8 production, PGE₂ acted as a negative regulator. Taken together, thrombin may play an important role in communication between blood coagulation and inflammation by inducting IL-8 production by monocytes and this role for thrombin may be further regulated by lymphokines and lipid mediators.