The proteasome regulates bacterial CpG DNA-induced signaling pathways in murine macrophages.

Our previous work has provided strong evidence that the proteasome is central to most of the genes induced in mouse macrophages in response to LPS stimulation. In the studies presented here, we evaluated the role of the macrophage proteasome in response to a second microbial product CpG DNA (unmethylated bacterial DNA). For these studies, we applied Affymetrix microarray analysis of RNA derived from murine macrophages stimulated with CpG DNA in the presence or absence of proteasome inhibitor, lactacystin. The results of these studies revealed that similar to LPS, most of those macrophage genes regulated by CpG DNA are also under the control of the proteasome at 4 h. In contrast to LPS stimulation, however, many of these genes were induced much later than 4 h, at 18 h, in response to CpG DNA. Lactacystin treatment of macrophages completely blocked the CpG DNA-induced gene expression of TNF-α and other genes involved in the production of inflammatory mediators. These data strongly support the conclusion that similar to LPS, the macrophage proteasome is a key regulator of CpG DNA-induced signaling pathways.