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Infection and Immunity, January 2005, p. 403-412, Vol. 73, No. 1
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.1.403-412.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Christel van den Hoogen,
Wilhelmina C. E. van Haaften, and
Vernon L. Tesh*
Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, Texas
Received 25 June 2004/ Returned for modification 14 September 2004/ Accepted 23 September 2004
Infections with Shiga toxin (Stx)-producing bacteria are associated with bloody diarrhea and postdiarrheal sequelae, including hemolytic uremic syndrome and central nervous system (CNS) abnormalities. Stx-induced intestinal, renal, and CNS vascular lesions may involve a localized production of proinflammatory cytokines in target organs, as tumor necrosis factor-
(TNF-
) and interleukin-1ß (IL-1ß) up-regulate Stx receptor globotriaosylceramide (Gb3) expression on vascular endothelial cells. However, leukocyte recruitment to injured sites may also exacerbate vascular damage. A cytokine macroarray analysis of transcripts derived from macrophage-like THP-1 cells treated with Stx1, lipopolysaccharides (LPS), or both demonstrated a consistent up-regulation of TNF-
, IL-1ß, and four genes encoding the chemokines interleukin-8 (IL-8), macrophage inflammatory protein-1
(MIP-1
), MIP-1ß, and growth-related oncogene beta (GRO-ß). Real-time PCR analysis verified the macroarray results. Northern blot analyses after the addition of the transcriptional inhibitor actinomycin D revealed increased IL-8 mRNA stability in THP-1 cells treated with Stx1 or Stx1 plus LPS. Finally, enzyme-linked immunosorbent assay data for Stx1- plus LPS-treated cells demonstrated a poor correlation between IL-8, MIP-1
, MIP-1ß, and GRO-ß mRNA levels and protein production, indicating a posttranscriptional regulatory effect. Our data suggest that in response to Stx1 and LPS, macrophages may be a source of chemokines that promote tissue damage through leukocyte recruitment and activation.
Present address: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.
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