This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cho, N.-H.
Right arrow Articles by Kim, I.-s.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cho, N.-H.
Right arrow Articles by Kim, I.-s.

 Previous Article  |  Next Article 

Infection and Immunity, September 2002, p. 4841-4850, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4841-4850.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction of the Gene Encoding Macrophage Chemoattractant Protein 1 by Orientia tsutsugamushi in Human Endothelial Cells Involves Activation of Transcription Factor Activator Protein 1

Nam-Hyuk Cho, Seung-Yong Seong, Myung-Sook Huh, Na-Hyun Kim, Myung-sik Choi, and Ik-sang Kim*

Department of Microbiology and Immunology, Seoul National University College of Medicine, and Institute of Endemic Disease, Seoul National University Medical Research Center, Chongno-gu, Seoul 110-799, Republic of Korea

Received 6 September 2001/ Returned for modification 4 January 2002/ Accepted 2 May 2002

Human macrophage chemoattractant protein 1 (MCP-1) is a potent mediator of macrophage migration and therefore plays an essential role in early events of inflammation. In endothelial cells, at least three independent pathways regulate MCP-1 expression by NF-{kappa}B and AP-1. Orientia tsutsugamushi causes vasculitis in humans by replicating inside macrophages and endothelial cells. In the present study, we investigated the cis-acting and trans-acting elements involved in O. tsutsugamushi-induced MCP-1 gene expression in human umbilical vein endothelial cells (HUVEC). Although NF-{kappa}B activation was observed in HUVEC infected with O. tsutsugamushi, inhibition of NF-{kappa}B activation did not affect the MCP-1 expression. However, treatment of HUVEC with extracellular signal-regulated kinase (ERK) kinase inhibitor or p38 mitogen-activated protein kinase (MAPK) inhibitor suppressed expression of MCP-1 mRNA concomitant with downregulation of activator protein 1 (AP-1) activation. Deletion of triphorbol acetate response elements (TRE) at position -69 to -63 of MCP-1 gene abolished inducible promoter activity. Deletion of TRE at position -69 to -63-96 to -90 or deletion of NF-{kappa}B-binding site at position -69 to -63-88 to -79 did not affect the inducibility of promoter. Site-directed mutagenesis of the NF-{kappa}B binding sites at positions -2640 to -2632, -2612 to -2603 in the enhancer region, or the AP-1 biding site at position -2276 to -2270 decreased the inducible activity of the promoter. Taken together, AP-1 activation by both the ERK pathway and the p38 MAPK pathway as well as their binding to TRE at position -69 to -63 in proximal promoter and TRE at position -2276 to -2270 in enhancer region is altogether essential in induction of MCP-1 mRNA in HUVEC infected with O. tsutsugamushi. Although NF-{kappa}B activation is not essential per se, the {kappa}B site in the enhancer region is important in MCP-1 induction of HUVEC. This discrepancy in the involvement of the NF-{kappa}B may be due to the function of chromatin structures and other transcription cofactors in the regulation of MCP-1 gene expression in response to O. tsutsugamushi infectioin.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. Phone: 82-2-740-8304. Fax: 82-2-743-0881. E-mail: molecule{at}plaza.snu.ac.kr.

Editor: R. N. Moore

Infection and Immunity, September 2002, p. 4841-4850, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4841-4850.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hisatsune, J., Nakayama, M., Isomoto, H., Kurazono, H., Mukaida, N., Mukhopadhyay, A. K., Azuma, T., Yamaoka, Y., Sap, J., Yamasaki, E., Yahiro, K., Moss, J., Hirayama, T. (2008). Molecular Characterization of Helicobacter pylori VacA Induction of IL-8 in U937 Cells Reveals a Prominent Role for p38MAPK in Activating Transcription Factor-2, cAMP Response Element Binding Protein, and NF-{kappa}B Activation. J. Immunol. 180: 5017-5027 [Abstract] [Full Text]  
  • Caselli, E., Fiorentini, S., Amici, C., Di Luca, D., Caruso, A., Santoro, M. G. (2007). Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-{kappa}B pathway. Blood 109: 2718-2726 [Abstract] [Full Text]  
  • Marra, F., Delogu, W., Petrai, I., Pastacaldi, S., Bonacchi, A., Efsen, E., Aleffi, S., Bertolani, C., Pinzani, M., Gentilini, P. (2004). Differential requirement of members of the MAPK family for CCL2 expression by hepatic stellate cells. Am. J. Physiol. Gastrointest. Liver Physiol. 287: G18-G26 [Abstract] [Full Text]  
  • Drevets, D. A., Leenen, P. J. M., Greenfield, R. A. (2004). Invasion of the Central Nervous System by Intracellular Bacteria. Clin. Microbiol. Rev. 17: 323-347 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»