Schematic diagram of the proposed pathway of LPS-SREC-I-TLR4 mediated activation of proinflammatory cytokine expression.

<p>This cartoon depicts LPS binding to SREC-I (1) followed by LPS-SREC-I complex recruitment of TLR4 into discrete lipid microdomains (thick line) (2). Localization of LPS-SREC-I-TLR4 complexes to such lipid microdomains then led to activation of downstream proinflammatory cytokine release through adaptor proteins MyD88 and TRIF. LPS exposure could thus mediate activation of the NF-kB and MAPK pathways. In addition, LPS has been shown to be recognized by CD14, the primary responder to the endotoxin, which then bound to TLR4 and triggered proinflammatory signaling through NF-kB and MAPK (3). We have additionally shown that LPS-SREC-I-TLR4 signaling led to activation of IRF3. Engagement of these signaling pathways could then lead to activation of transcription factors NF-kB, AP-1 and IRF3 that have been shown to function combinatorially in cytokine gene transcription.