Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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
StatePublished - Dec 1 1999
Externally publishedYes

Fingerprint

Monocytes
Atopic Dermatitis
Granulocyte-Macrophage Colony-Stimulating Factor
Apoptosis
Exotoxins
Cytokines
Macrophage Colony-Stimulating Factor
Interleukin-1
Macrophages
Skin
Conditioned Culture Medium
Coculture Techniques
Staphylococcal enterotoxin F
Neutralizing Antibodies
Staphylococcus aureus
Enzyme-Linked Immunosorbent Assay
Tissue Donors
Survival
DNA
Incidence

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bratton, D. L., May, K. R., Kailey, J. M., Doherty, D. E., & Leung, D. Y. M. (1999). Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis. Journal of Allergy and Clinical Immunology, 103(5 II), 895-900.

Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis. / Bratton, Donna L.; May, Kathleen Ruffing; Kailey, Jenai M.; Doherty, Dennis E.; Leung, Donald Y.M.

In: Journal of Allergy and Clinical Immunology, Vol. 103, No. 5 II, 01.12.1999, p. 895-900.

Research output: Contribution to journalArticle

Bratton, DL, May, KR, Kailey, JM, Doherty, DE & Leung, DYM 1999, 'Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis', Journal of Allergy and Clinical Immunology, vol. 103, no. 5 II, pp. 895-900.
Bratton, Donna L. ; May, Kathleen Ruffing ; Kailey, Jenai M. ; Doherty, Dennis E. ; Leung, Donald Y.M. / Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis. In: Journal of Allergy and Clinical Immunology. 1999 ; Vol. 103, No. 5 II. pp. 895-900.
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AB - 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.

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