Secretion of IL-6, IL-8 and G-CSF by human endothelial cells in vitro in response to Staphylococcus aureus and staphylococcal exotoxins.
The capacity of endothelial cells to produce and release cytokines (IL-6, IL-8 and G-CSF) in response to exposure to Staphylococcus aureus strains or staphylococcal exotoxins (alpha-toxin, enterotoxin A and TSST-1) was investigated. An endothelial cell culture model of human umbilical vein endothelial cells (HUVEC) was used. Five out of ten clinical isolates of S. aureus were found to induce cytokine production and release from endothelial cells. Four of the five isolates that induce cytokine release produced enterotoxin A, B, C, D and/or TSST-1, compared with two of those that did not induce release. Purified staphylococcal exotoxins (1 pg/ml-1 microg/ml) did not act as primary stimuli and induced no detectable cytokine secretion. When endothelial cells were prestimulated with IL-1beta or TNF alpha at a concentration of 1 ng/ml for 2 h, IL-1beta served as a potent primary stimulus for IL-6, IL-8 and G-CSF production, whereas TNF alpha did not induce any significant cytokine release during the subsequent 24 h. A further increase in IL-6 and G-CSF release, but not of IL-8, was observed when IL-1beta prestimulated cells were exposed to alpha-toxin or TSST-1. However, to potentiate cytokine production (IL-6 and IL-8) by SEA, both IL-1beta and the toxin had to be present simultaneously. Our data show that S. aureus, but not staphylococcal exotoxins, have the capacity to act as primary stimuli of endothelial cells and induce production and release of cytokines. IL-1beta may prime HUVEC to release IL-6, IL-8 and G-CSF prior to subsequent stimulation with staphylococcal exotoxins.
Department of Infectious Diseases, Orebro Medical Center Hospital, Sweden.
B
B
Söderquist
J
J
Källman
H
H
Holmberg
T
T
Vikerfors
E
E
Kihlström
D001427:Bacterial Toxins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology; D005098:Exotoxins / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C021091:staphylococcal alpha-toxin; D016179:Granulocyte Colony-Stimulating Factor; C026066:enterotoxin A, Staphylococcal