Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis

Donna L. Bratton, Kathleen R. May, Jenai M. Kailey, Dennis E. Doherty, Donald Y.M. Leung

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background: Chronic atopic dermatitis (AD) lesions are associated with colonization by exotoxin-producing Staphylococcus aureus. Evidence suggests that cytokine production in AD, particularly of GM-CSF, prolongs survival of both peripheral blood monocytes and dermal monocyte-macrophages, the predominate inflammatory cell in lesions caused by chronic AD. Objective: We sought to determine whether the staphylococcal exotoxin, toxic shock syndrome toxin-1 (TSST-1), could stimulate prosurvival cytokine production in monocytes and thereby inhibit apoptosis. Methods: Cultures of peripheral blood monocytes from normal donors and subjects with AD were incubated with various concentrations of TSST-1, and the incidence of apoptosis was assessed by examining cytospin preparations and the appearance of hypodiploid DNA in the flow cytometer. Culture supernatants were analyzed for GM-CSF, IL-1β, and TNF-α by ELISA. Results: TSST-1, in a concentration-dependent manner starting at 0.1 pg/mL, significantly inhibited monocyte apoptosis and resulted in the production of the prosurvival cytokines GM-CSF, IL-1, and TNF-α. In coculture conditions with conditioned media from TSST-1-stimulated monocytes, with or without neutralizing antibody to the various cytokines, the data show GM-CSF production was responsible for the inhibition of apoptosis. Conclusions: The data strongly suggest that staphylococcal exotoxins known to colonize skin lesions on patients with chronic AD may induce the production of GM-CSF, resulting in inhibition of monocyte-macrophage apoptosis, and thereby contribute to the chronicity of this inflammatory disease.

Original languageEnglish (US)
Pages (from-to)895-900
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume103
Issue number5 II
DOIs
StatePublished - 1999

Keywords

  • Apoptosis
  • Atopic dermatitis
  • Granulocyte-macrophage colony-stimulating factor
  • Monocyte
  • Staphylococcal exotoxins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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