Staphylococcal enterotoxin B inhibits the production of interleukin-4 in a human mast-cell line HMC-1

Staphylococcal enterotoxins belong to the recently characterized group of immunocytotropic bacterial superantigens that are potent mitogens for human T cells. Superantigens are presented, but without intracellular processing, to T cells by monocyte/macrophages, Langerhans' cells and keratinocytes via the class II major histocompatibility complex (MHC) molecules. Superantigens have been demonstrated to act as potent inducers of several proinflammatory cytokines in the antigen-presenting cells such as interleukin-l (IL-l) and tumour necrosis factor-a (TNF-ar). As mast cells participate in the pathogenesis of several inflammatory skin disorders such as atopic dermatitis (AD), which is often aggravated by staphylococcal infections, we studied the effect of staphylococcal enterotoxin B (SEB) superantigen on the histamine release and IL-4 expression in a human mast-cell line (HMC-1). Incubation of SEE (50 mu g/ml) with HMC-1 cells for 45 min, could not induce any histamine release. The HMC-1 cells were also stimulated with various concentrations of SEE (0, 1, 10, 20, 50 mu g/ml) for 1, 2, 3 and 4 days. Clear dose-dependent inhibition of IL-4 protein production and release was observed on day 4 without any observed effect on cell viability. Compared with unstimulated HMC-1 cells, after 50 mu g/ml SEE stimulation, the IL-4 mRNA levels decreased steadily in the 2, 6, 18 and 24 hr samples in repeated experiments as measured with the reverse transcription-polymerase chain reaction (RT-PCR) method. In comparison, a biphasic decrease in TNF-alpha expression was found. Our results show that in human leukaemic mast cells, superantigen stimulation downregulates the production of IL-4.