TY - JOUR
T1 - Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis
AU - Bratton, Donna L.
AU - May, Kathleen R.
AU - Kailey, Jenai M.
AU - Doherty, Dennis E.
AU - Leung, Donald Y.M.
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - 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.
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.
KW - Apoptosis
KW - Atopic dermatitis
KW - Granulocyte-macrophage colony-stimulating factor
KW - Monocyte
KW - Staphylococcal exotoxins
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U2 - 10.1016/s0091-6749(99)70435-5
DO - 10.1016/s0091-6749(99)70435-5
M3 - Article
C2 - 10329825
AN - SCOPUS:0033033445
SN - 0091-6749
VL - 103
SP - 895
EP - 900
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5 II
ER -