Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells.
BACKGROUND
Staphylococcus aureus produces a set of proteins which act both as superantigens and toxins. Although their mode of action as superantigens is well understood, little is known about their effects on airway epithelial cells.


METHODS
To investigate this problem, primary nasal epithelial cells derived from normal and asthmatic subjects were stimulated with staphylococcal enterotoxin A and B (SEA and SEB) and secreted (supernatants) and cell-associated (cell lysates) IL-8, TNF-alpha, RANTES and eotaxin were determined by specific ELISAs.


RESULTS
Non-toxic concentrations of SEA and SEB (0.01 microg/ml and 1.0 microg/ml) induced IL-8 secretion after 24 h of culture. Pre-treatment of the cells with IFN-gamma (50 IU/ml) resulted in a further increase of IL-8 secretion. In cells from healthy donors pretreated with IFN-gamma, SEA at 1.0 mug/ml induced release of 1009 pg/ml IL-8 (733.0-1216 pg/ml, median (range)) while in cells from asthmatic donors the same treatment induced significantly higher IL-8 secretion - 1550 pg/ml (1168.0-2000.0 pg/ml p = 0.04). Normal cells pre-treated with IFN-gamma and then cultured with SEB at 1.0 mug/ml released 904.6 pg/ml IL-8 (666.5-1169.0 pg/ml). Cells from asthmatics treated in the same way produced significantly higher amounts of IL-8--1665.0 pg/ml (1168.0-2000.0 pg/ml, p = 0.01). Blocking antibodies to MHC class II molecules added to cultures stimulated with SEA and SEB, reduced IL-8 secretion by about 40% in IFN-gamma unstimulated cultures and 75% in IFN-gamma stimulated cultures. No secretion of TNF-alpha, RANTES and eotaxin was noted.


CONCLUSIONS
Staphylococcal enterotoxins may have a role in the pathogenesis of asthma.
O'Brien
Garrett J
GJ
Respiratory Research Group, School of Medicine and Dentistry, Queen's University Belfast, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK. obriengarrett@yahoo.ie
Riddell
Gareth
G
Elborn
J Stuart
JS
Ennis
Madeleine
M
Skibinski
Grzegorz
G
D000328:Adult; D001249:Asthma / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013997:Time Factors
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016209:Interleukin-8; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma