Effects of trichothecene structure on cytokine secretion and gene expression in murine CD4+ T-cells
| Autor: | James J. Pestka, Juan I. Azcona-Olivera, Yan L. Ouyang |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
CD4-Positive T-Lymphocytes
Interleukin 2 Transcription Genetic Acylation Trichothecene Enzyme-Linked Immunosorbent Assay Toxicology medicine.disease_cause Mice Structure-Activity Relationship chemistry.chemical_compound Vomitoxin Gene expression Concanavalin A medicine Animals RNA Messenger Cells Cultured Antibiotics Antineoplastic biology Toxin Verrucarin A Molecular biology Blotting Southern T-2 Toxin Gene Expression Regulation chemistry Immunology biology.protein Cytokines Interleukin-2 Cytokine secretion Interleukin-4 Interleukin-5 Trichothecenes medicine.drug |
| Zdroj: | Toxicology. 104:187-202 |
| ISSN: | 0300-483X |
| DOI: | 10.1016/0300-483x(95)03147-8 |
| Popis: | The effects of trichothecene structure on cytokine secretion and gene expression were assessed in primary CD4 + T-cells from murine spleen. CD4 + T-cells were stimulated with concanavalin A (Con A) for 2 or 7 days in the presence of various concentrations of the trichothecenes, vomitoxin (VT or deoxynivalenol), nivalenol (NIV), 15-acetyl deoxynivalenol (15-ADON), 3-acetyl deoxynivalenol (3-ADON), T-2 toxin (T-2) and verrucarin A (Ver A). Culture supernatants were subsequently analyzed for interleukin (IL)-2, IL-4 and IL-5 by ELISA. At day 2, all trichothecenes were found to have inhibited production of IL-2, IL-4, and IL-S. However, at day 7, supernatant IL-2 was significantly increased (2–5.5-fold) in cultures containing VT, NIV, 3-ADON, and 15-ADON at 250, 250, 2500, and 1000 ng/ml doses, respectively, when compared to control Con A-stimulated cultures; significant increases in IL-2 were not observed with T-2 and Ver-A. Similarly, at day 7, IL-4 and IL-5 were significantly increased in the presence of VT (100 ng/ml), NIV (100 ng/ml), 3-ADON (1000 ng/ml), 15-ADON (500 ng/ml), T-2 (1 ng/ml), and Ver A (50 pg/ml, only IL-5) when compared to control cultures. IL production was inhibited at trichothecene concentrations exceeding the aforementioned optima. When total RNA of 2-day cultures was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) in conjunction with Southern analysis, IL-2 mRNA was also found to be superinduced by VT (50 and 100 ng/ml), NIV (50, 100 and 250 ng/ml), 3-ADON (1500 ng/ml), 15-ADON (100 ng/ml), T-2 (0.5 ng/ml) and Ver A (25, 50 and 100 pg/ml); IL-4 mRNA by VT (50 ng/ml), NIV (50 ng/ml), and Ver A (25, 50 and 100 pg/ml); IL-5 mRNA by VT (50 ng/ml); and IL-6 mRNA by 15-ADON (100 ng/ml) and Ver A (50 pg/ml). As the trichothecene concentration increased from these levels, inhibition of mRNA transcript levels was also observed for many of the interleukins. Taken together, the results suggest that trichothecenes as a group can either inhibit or superinduce both IL secretion and mRNA levels in CD4 + T-cells. Superinduction exhibited a rank order of macrocyclic > type A > type B trichothecenes and was dependent on acylation of the trichothecene nucleus. |
| Databáze: | OpenAIRE |
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