Allergen challenge primes for IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics
| Autor: | P, Borger, G J, Jonker, E, Vellenga, D S, Postma, J G, De Monchy, H F, Kauffman |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes Isoproterenol Antibodies Monoclonal Allergens Middle Aged Lymphocyte Activation Asthma Bronchial Provocation Tests Dinoprostone Interferon-gamma Receptors Adrenergic beta Humans Female RNA Messenger Interleukin-5 Adenylyl Cyclases DNA Primers |
| Zdroj: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 29(7) |
| ISSN: | 0954-7894 |
| Popis: | In previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40-50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are differentially regulated by the AC system. Therefore, we postulate that an increased IL-5/IFN-gamma ratio as observed in asthmatics might be due to a dysfunctional AC system.To assess whether a dysfunctional AC system as observed in asthmatics after allergen provocation, is responsible for an increased IL-5/IFN-gamma cytokine ratio.Peripheral blood T lymphocytes of seven asthma patients were stimulated with anti-CD3 plus anti-CD28 MoAbs in the absence and presence of isoproterenol (ISO) and prostaglandin E2 (PGE2) to activate the AC system. Before, 3 h and 24 h after allergen provocation, IFN-gamma and IL-5 mRNAs were detected by semiquantitative RT-PCR.Before allergen provocation, ISO (10-5 mol/L) significantly downregulated IFN-gamma mRNA (P0.03, n = 6), and showed a trend to upregulate IL-5 mRNA (P = 0.138, n = 5). Three and 24 h after allergen provocation, ISO was not longer able to modulate IFN-gamma and IL-5. In contrast with the observations with ISO, PGE2 still dose-dependently inhibited IFN-gamma mRNA, both before, 3 h and 24 h after allergen provocation (n = 7). IL-5 mRNA, but not IFN-gamma mRNA, was significantly upregulated in anti-CD3 plus anti-CD28-activated T cells (P0.05, n = 5) 24 h after allergen provocation, compared with before allergen provocation.Twenty-four hours after allergen provocation, a significant reduction of beta-adrenergic control on IFN-gamma and IL-5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL-5 mRNA production. |
| Databáze: | OpenAIRE |
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