Figure 6.

Regulation of IL-8 expression by LPS and FnIII domains. The model depicts the activation of TLR4 signaling in response to LPS and FnIII domains. LPS binds to both CD14, a GPI-linked protein, and MD2, a TLR4-associated protein. The interaction of LPS with these molecules triggers TLR4 dimerization and activation of downstream signaling to NF-κB and mitogen-active protein kinase pathways such as ERK. Activation of the NF-κB and AP1 transcription factors then induces the expression of IL-8 mRNA and protein synthesis. EGFR and Src kinases have been demonstrated to regulate the TLR4-dependent release of cytokines by LPS. The current study has now implicated Src and EGFR in cytokine release in response to FnIII domains. The specific roles of Src kinases and EGFR in TLR4 activation and signaling are not well understood. Possible interrelationships are depicted by dotted lines. The molecule labeled with a question mark (?) represents possible binding partners for FnIII domains that might participate in TLR4 activation. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound