Expression of chemokine genes in murine macrophages infected with Orientiatsutsugamushi

Scrub typhus, caused by Orientia tsutsugamushi infection, is characterized by local as well as systemic inflammatory manifestations. Inflammation is i nitiated by O. tsutsugamushi-infected macrophages and endothelial cells in the dermis. We investigated the regulation of chemokine induction in macrop hage cell line J774A.1 in response to O. tsutsugamushi infection, The mRNAs for macrophage inflammatory proteins 1 alpha/beta (MIP-1 alpha/beta), 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 lymphota ctin, eotaxin, gamma interferon-inducible protein 10, and T-cell activation gene 3 mRNAs were not detected by RNase protection assays. seat-killed O. tsutsugamushi induced a similar extent of chemokine responses. Induction of the chemokine genes was not blocked by the eukaryotic protein synthesis in hibitor cycloheximide, suggesting that de novo synthesis of host cell prote in is not required for these transcriptional responses. The induction of ch emokine mRNAs by O. tsutsugamushi was blocked by the inhibitors of NF-kappa B activation. Furthermore, O, tsutsugamushi induced the nuclear translocat ion and activation of NF-kappa B. These results demonstrate that heat-stabl e molecules of O. tsutsugamushi induce a subset of chemokine genes and that induction involves activation of the transcription factor NF-kappa B.