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Infection and Immunity, February 2000, p. 594-602, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Expression of Chemokine Genes in Murine Macrophages
Infected with Orientia tsutsugamushi
Nam-Hyuk
Cho,1
Seung-Yong
Seong,1,*
Myung-Suk
Huh,1
Tae-Hee
Han,2
Young-Sang
Koh,3
Myung-Sik
Choi,1 and
Ik-Sang
Kim1
Department of Microbiology, Seoul National
University College of Medicine, Seoul 110-799,1
Department of Microbiology and Immunology, Sungkyunkwan University
School of Medicine, Suwon 440-746,2 and
Department of Microbiology, Cheju National University College of
Medicine, Cheju 690-756,3 Republic of
Korea
Received 9 August 1999/Returned for modification 10 September
1999/Accepted 4 November 1999
Scrub typhus, caused by Orientia tsutsugamushi
infection, is characterized by local as well as systemic inflammatory
manifestations. Inflammation is initiated by O. tsutsugamushi-infected macrophages and endothelial cells in the
dermis. We investigated the regulation of chemokine induction in
macrophage cell line J774A.1 in response to O. tsutsugamushi infection. The mRNAs for macrophage inflammatory proteins 1
/
(MIP-1
/
), 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-killed O. tsutsugamushi induced 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 by O. tsutsugamushi was blocked by the inhibitors of NF-
B
activation. Furthermore, O. tsutsugamushi induced the
nuclear translocation and activation of NF-
B. These results
demonstrate that heat-stable molecules of O. tsutsugamushi
induce a subset of chemokine genes and that induction involves
activation of the transcription factor NF-
B.
*
Corresponding author. Mailing address: Department of
Microbiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. Phone:
82-2-740-8301. Fax: 82-2-743-0881. E-mail:
seongsy{at}plaza.snu.ac.kr.
Infection and Immunity, February 2000, p. 594-602, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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