Global transcriptional response of macrophage-like THP-1 cells to Shiga toxin type

Dinorah Leyva-Illades, Rama P. Cherla, Cristi L. Galindo, Ashok Chopra, Vernon L. Tesh

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Shiga toxins (Stxs) are bacterial cytotoxins produced by the enteric pathogens Shigella dysenteriae serotype 1 and some serotypes of Escherichia coli that cause bacillary dysentery and hemorrhagic colitis, respectively. To date, approaches to studying the capacity of Stxs to alter gene expression in intoxicated cells have been limited to individual genes. However, it is known that many of the signaling pathways activated by Stxs regulate the expression of multiple genes in mammalian cells. To expand the scope of analysis of gene expression and to better understand the underlying mechanisms for the various effects of Stxs on host cell functions, we carried out comparative microarray analyses to characterize the global transcriptional response of human macrophage-like THP-1 cells to Shiga toxin type 1 (Stx1) and lipopolysaccharides. The data were analyzed by using a rigorous combinatorial approach with three separate statistical algorithms. A total of 36 genes met the criteria of upregulated expression in response to Stx1 treatment, with 14 genes uniquely upregulated by Stx1. Microarray data were validated by real-time reverse transcriptase PCR for genes encoding early growth response 1 (Egr-1) (transcriptional regulator), cyclooxygenase 2 (COX-2; inflammation), and dual specificity phosphatase 1 (DUSP1), DUSP5, and DUSP10 (regulation of mitogen-activated protein kinase signaling). Stx1-mediated signaling through extracellular signal-regulated kinase 1/2 and Egr-1 appears to be involved in the increased expression and production of the proinflammatory mediator tumor necrosis factor alpha. Activation of COX-2 is associated with the increased production of proinflammatory and vasoactive eicosanoids. However, the capacity of Stx1 to increase the expression of genes encoding phosphatases suggests that mechanisms to dampen the macrophage proinflammatory response may be built into host response to the toxins.

Original languageEnglish (US)
Pages (from-to)2454-2465
Number of pages12
JournalInfection and Immunity
Volume78
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Shiga Toxin 1
Shiga Toxin
Shiga Toxins
Macrophages
Gene Expression
Genes
Dual Specificity Phosphatase 1
Shigella dysenteriae
Bacillary Dysentery
Mitogen-Activated Protein Kinase 3
Eicosanoids
Mitogen-Activated Protein Kinase 1
Cytotoxins
Cyclooxygenase 2
Colitis
Microarray Analysis
Growth
Mitogen-Activated Protein Kinases
Reverse Transcriptase Polymerase Chain Reaction
Phosphoric Monoester Hydrolases

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Global transcriptional response of macrophage-like THP-1 cells to Shiga toxin type. / Leyva-Illades, Dinorah; Cherla, Rama P.; Galindo, Cristi L.; Chopra, Ashok; Tesh, Vernon L.

In: Infection and Immunity, Vol. 78, No. 6, 06.2010, p. 2454-2465.

Research output: Contribution to journalArticle

Leyva-Illades, Dinorah ; Cherla, Rama P. ; Galindo, Cristi L. ; Chopra, Ashok ; Tesh, Vernon L. / Global transcriptional response of macrophage-like THP-1 cells to Shiga toxin type. In: Infection and Immunity. 2010 ; Vol. 78, No. 6. pp. 2454-2465.
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