Expression of Chemokine Genes in Murine Macrophages Infected withOrientia tsutsugamushi

Scrub typhus, caused byOrientia tsutsugamushiinfection, is characterized by local as well as systemic inflammatory manifestations. Inflammation is initiated byO. tsutsugamushi-infected macrophages and endothelial cells in the dermis. We investigated the regulation of chemokine induction in macrophage cell line J774A.1 in response toO. tsutsugamushiinfection. The mRNAs for macrophage inflammatory proteins 1α/β (MIP-1α/β), MIP-2, and macrophage chemoattractant protein 1 were induced within 30 min, and their levels showed a transitory peak for 3 to 12 h. However, the lymphotactin, eotaxin, gamma interferon-inducible protein 10, and T-cell activation gene 3 mRNAs were not detected by RNase protection assays. Heat-killedO. tsutsugamushiinduced a similar extent of chemokine responses. Induction of the chemokine genes was not blocked by the eukaryotic protein synthesis inhibitor cycloheximide, suggesting that de novo synthesis of host cell protein is not required for these transcriptional responses. The induction of chemokine mRNAs byO. tsutsugamushiwas blocked by the inhibitors of NF-κB activation. Furthermore,O. tsutsugamushiinduced the nuclear translocation and activation of NF-κB. These results demonstrate that heat-stable molecules ofO. tsutsugamushiinduce a subset of chemokine genes and that induction involves activation of the transcription factor NF-κB.