Chemokine expression in the monocytic cell line THP-1 in response to purified shiga toxin 1 and/or lipopolysaccharides.

Abstract

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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) up-regulate Stx receptor globotriaosylceramide (Gb(3)) 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-alpha, IL-1beta, and four genes encoding the chemokines interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and growth-related oncogene beta (GRO-beta). 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-1alpha, MIP-1beta, and GRO-beta 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.

• Authors: Lisa M Harrison, Christel van den Hoogen, Wilhelmina C E van Haaften, Vernon L Tesh
• Journal: Infection and immunity (Infect Immun) Vol. 73 Issue 1 Pg. 403-12 (Jan 2005) ISSN: 0019-9567 [Print] United States
• PMID: 15618178 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CCL3
• Chemokine CCL4
• Chemokines
• Cytokines
• Interleukin-8
• Lipopolysaccharides
• Macrophage Inflammatory Proteins
• Shiga Toxin 1

Topics

• Cell Line, Tumor
• Chemokine CCL3
• Chemokine CCL4
• Chemokines (genetics)
• Cytokines (genetics)
• Humans
• Interleukin-8 (biosynthesis, genetics)
• Lipopolysaccharides (pharmacology)
• Macrophage Inflammatory Proteins (biosynthesis)
• Oligonucleotide Array Sequence Analysis
• Polymerase Chain Reaction
• Shiga Toxin 1 (pharmacology)