Staphylococcal Enterotoxin B Upregulates Fas‐Mediated Apoptosis of Peripheral Blood Mononuclear Cells in Childhood Atopic Dermatitis

Abstract

Staphylococcal infection-producing superantigens, such as staphylococcal enterotoxin B (SEB), are presumed to play an important role of inflammatory processes in atopic dermatitis (AD). The aim of this study was to elucidate the apoptotic response of peripheral blood mononuclear cells (PBMCs) from children with AD. PBMCs from AD children were sampled and cultured with SEB stimulation. Levels of apoptosis and Fas expression were measured using flow cytometry; the soluble Fas ligand (sFasL) was also measured using the enzymelinked immunosorbent assay method, and the expression of FasL in PBMCs was observed using reverse transcriptase-polymerase chain reaction. There was no difference in the initial levels of apoptosis and Fas expression in precultured PBMCs of AD patients and healthy donors. After culturing for 48 h under SEB stimulation, the apoptosis level and Fas expression were significantly upregulated in the PBMCs from AD children compared with that from the normal controls. In patients, the sFasL was significantly increased, and the expression of FasL was observed in messenger RNA of peripheral monocytes. These results suggest that the Fas/FasL system is involved in the apoptosis induced by SEB in AD, with simultaneous increases in sFasL and expression of FasL.

Modeling the effects of a Staphylococcal Enterotoxin B (SEB) on the apoptosis pathway

“…First, several factors could be causing an increase in FasL concentration. Specifically, both SEB treatment of various cell types (including Jurkats) and activation of the Fas receptor [ 13 , 14 ] have been shown to cause the de novo production and secretion of soluble FasL (sFasL). Also, SEB treatment has been shown to induce the production of several members of the (tumor necrosis factor) TNF superfamily such as TNFα and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) [ 11 ].…”

“…Apoptosis is a naturally occurring mechanism by which a cell undergoes programmed death in response to external or internal signals. It has been shown that many potential biowarfare agents including Staphylococcal Enterotoxin B (SEB) improperly activate the pathways controlling this process in a variety of cell types [ 1 - 4 ]. These agents target specific components of these pathways, inducing a cascade of reactions that modify the rate at which apoptosis occurs.…”

“…Since the induction of apoptosis underlies the lethality of SEB, this pathway presents a good target for therapeutic intervention. Previous results have shown that SEB treatment affects the expression of proteins involved in the Fas-mediated apoptotic pathway [ 2 , 4 ]. However, the mechanisms by which these agents interact with this pathway, and the cellular components most advantageous for potential therapies, is unclear.…”

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Background The lack of detailed understanding of the mechanism of action of many biowarfare agents poses an immediate challenge to biodefense efforts. Many potential bioweapons have been shown to affect the cellular pathways controlling apoptosis [ 1 - 4 ]. For example, pathogen-produced exotoxins such as Staphylococcal Enterotoxin B (SEB) and Anthrax Lethal Factor (LF) have been shown to disrupt the Fas-mediated apoptotic pathway [ 2 , 4 ].

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“…Many potential bioweapons have been shown to affect the cellular pathways controlling apoptosis [ 1 - 4 ]. For example, pathogen-produced exotoxins such as Staphylococcal Enterotoxin B (SEB) and Anthrax Lethal Factor (LF) have been shown to disrupt the Fas-mediated apoptotic pathway [ 2 , 4 ]. To evaluate how these agents affect these pathways it is first necessary to understand the dynamics of a normally functioning apoptosis network.…”