In addition to its central role in blood coagulation and hemostasis, human alpha-thrombin is a powerful regulator of inflammatory responses and is known to affect cell-mediated immunity. Interleukin (IL)-12 is a strong promoter of the development of Th1-type lymphocytes and its downregulation implies a positive feedback mechanism for development of Th2 responses. We have previously shown that thrombin enhances the release of IL-6, a Th2-related cytokine, in human peripheral blood mononuclear cells (PBMC). Here we show that thrombin downregulates IL-12 production at both protein and mRNA levels in human PBMC. The inhibition of IL-12 production was accompanied by an enhanced release of IL-10, which inhibits Th1-related processes and promotes Th2-type responses. The use of proteolytically inactive thrombin and of the specific thrombin receptor agonist peptide, SFLLRN, reveals that this downregulation is thrombin-specific and requires thrombin proteolytic activity. In addition, activation of coagulation inhibits IL-12 production in whole blood cultures, confirming the tight relationship between the coagulation pathway, where thrombin is a key enzyme, and inflammation. Decreased IL-12 production appears to be related also to IL-10 production, since the addition of an anti-IL-10 monoclonal antibody to thrombin-treated PBMC resulted in a partial restoration of IL-12 production. In conclusion, the observation that thrombin significantly affects the production of IL-12, as well as of IL-10, implies a concerted role orchestrated by thrombin in PBMC that could be crucial to effective immunity and inflammation.
Scheda prodotto non validato
Scheda prodotto in fase di analisi da parte dello staff di validazione
|Titolo:||Inhibition of interleukin-12 expression by alpha-thrombin in human peripheral blood mononuclear cells: a potential mechanism for modulating Th1/Th2 responses.|
|Citazione:||Naldini, A., L., A., Pucci, A., Bernini, C., & Carraro, F. (2003). Inhibition of interleukin-12 expression by alpha-thrombin in human peripheral blood mononuclear cells: a potential mechanism for modulating Th1/Th2 responses. BRITISH JOURNAL OF PHARMACOLOGY, 140(5), 980-986.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
File in questo prodotto:
|Inhibition of interleukin-12 expression by a-thrombin in human peripheral blood mononuclear cells a potential mechanism for modulating Th1 Th2 responses BritJPharm2003.pdf||Post-print||NON PUBBLICO - Accesso privato/ristretto||Administrator Richiedi una copia|