Induction of Human Monocyte Interleukin (IL)-8 by Fibrinogen through the Toll-Like Receptor Pathway
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Fibrinogen, in addition to its role in coagulation, is also an acute phase protein of inflammation. Treatment of adherent human monocytes with fibrinogen increases IL-8, IL-6, and TNF-α, but has no effect on MCP-1, IFN-β, or IP-10. Treatment of monocytes with fibrinogen and C5a doubles IL-8 and IL-6 production, compared to fibrinogen alone. The increase in cytokine production was accompanied by a transient increase in IL-8 mRNA and increased NF-κB activity. Monocytes from an IRAK-4- and two NEMO-deficient patients had 80% reduced IL-8 responses to fibrinogen. Moreover, responses to fibrinogen were blocked with anti-CD14 antibody (MY4), a subunit of the LPS receptor. The data indicate that fibrinogen alone and fibrinogen plus C5a are potent inducers of cytokine production in monocytes, and that signaling by fibrinogen is mediated through the TLR-4 pathway.
Key wordsmonocytes fibrinogen IL-8 Toll-like receptor
The authors thank Rhonda DaSilva and Danielle Fink for their excellent technical assistance. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade name, commercial products, or organization imply endorsements by the US Government.
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