Abstract
Enterotoxin B Induces Profound Expression of Inflammatory Cytokines and Chemokines D. A. Wagner, S. C. Shin, B. P. Tancowny, R. P. Schleimer, L. C. Grammer; Allergy and Immunology, Northwestern University, Chicago, IL. RATIONALE: Staphylococcal enterotoxins B (SEB) function as superantigens (Sag), stimulating lymphocytes to produce proinflammatory cytokines and chemokines. Since airways in chronic rhinosinusitis contain Sag, we investigated inflammatory responses of epithelial cells and lymphocytes triggered by SEB. METHODS: BEAS2B airway epithelial cells were cultured with/without purified T lymphocytes and stimulated with medium or SEB toxin (100ng/ml) after pretreatment with medium or interferon gamma (50ng/ml for 24 hours). Supernatants/mRNA were isolated/analyzed for the expression of chemokines, cytokines and inflammatory mediators using Cytokine Bead Array Assays and Taqman Real-Time PCR. RESULTS: Direct stimulation of BEAS2B cells with SEB did not induce chemokine expression and caused only a modest induction of B7-H1 and SAA (average 3.2, 1.3 fold control respectively, n=3). After pretreatment with interferon gamma a greater direct response of BEAS2B cells to SEB was evident (B7-H1 17 fold, SAA 129 fold control, n=3). Profound expression of chemokines & cytokines was observed when epithelial cells were co-cultured with purified T cells and 100ng/ml SEB (For IP-10: BEAS2B, 63 +/28 pg/ml; T cells, 106 +/17 pg/ml; BEAS2B + T cells, 360,000 +/67,000 pg/ml; P=0.0001. For MIG: BEAS2B, 9 +/5 pg/ml; T cells, 22 +/22 pg/ml; BEAS2B + T cells, 290,000 +/87,000 pg/ml; P=0.004. For TNF alpha: BEAS2B, 7 +/4 pg/ml; T cells, 247 +/104 pg/ml; BEAS2B + T cells, 799 +/324 pg/ml; P=0.05). CONCLUSIONS: These data suggest profound production of specific cytokines & chemokines is induced by Sag as a result of interactions between epithelial cells & T lymphocytes. Funding: Ernest S. Bazley Asthma and Allergic Diseases Center
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