Dissection of LPS-induced signaling pathways in murine macrophages using LPS analogs, LPS mimetics, and agents unrelated to LPS.

The model in Figure 3 summarizes the data presented above. Using the induction of the select panel of LPS-inducible genes and the phosphorylation on tyrosine of specific MAP kinases, we have been able to dissociate three signaling pathways shared by LPS and its analogs and mimetics: a pathway that leads to tyrosine phosphorylation, one that leads to the induction of a gene subset including TNF alpha, TNFR-2, and IL-1 beta, and a pathway that results in induction of IP-10, D3, and D8 gene expression. It is still unclear if macrophage activation by non-LPS products occurs entirely through distinct yet redundant pathways or if other signaling receptors ultimately tie into the same intermediate pathways. This approach may identify particular stimuli as tools to induce specific pathways leading to select gene subsets and/or tyrosine kinase activation and, perhaps, identify a pathway deficient in C3H/HeJ macrophages.