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Glucocorticoids up‐regulate constitutive interleukin‐10 production by human monocytes
Author(s) -
Mozo L.,
Suárez A.,
Gutiérrez C.
Publication year - 2004
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2004.01824.x
Subject(s) - glucocorticoid receptor , glucocorticoid , biology , antiglucocorticoid , monocyte , northern blot , endocrinology , medicine , ex vivo , interleukin , receptor , in vivo , messenger rna , immunology , cytokine , gene , biochemistry , microbiology and biotechnology
Summary Background IL‐10 plays an immunosuppressive role in inflammatory responses. Increased plasma levels of IL‐10 have been detected in patients under glucocorticoid (GC) therapy, indicating that steroids may exert their suppressive effect, in part, by increasing IL‐10 production. Objectives The aim was to define possible mechanisms by which steroids up‐regulate IL‐10 production. To this end, we have analysed ex vivo the effect of GCs on the constitutive production of IL‐10 by lymphocytes and cells of myeloid origin. Methods Monocytes and T cells were isolated by a Percoll gradient and B cells were purified by rosetting. Protein and mRNA IL‐10 levels were determined by ELISA and by Northern blot, respectively. Results Monocytes, but not T or B cells, up‐regulated the constitutive production of IL‐10 following pre‐treatment for at least 12 h with physiological doses of dexamethasone (Dex). Up‐regulation of IL‐10 occurred at both protein and mRNA levels, probably indicating that the effect of Dex was by incrementing gene transcription. Other steroids had similar outcomes, their effects being dose‐related, proportional to the steroid potency and totally reversed by the steroid antagonist RU486. Thus, transcript levels of IL‐10 were up‐regulated by GCs probably through binding of the GC receptor to its specific glucocorticoid response element sequence in the IL‐10 promoter. In contrast to monocytes, differentiated immature macrophages and dendritic cells did not vary their constitutive IL‐10 production after pre‐treatment with Dex. Conclusion Our results support the fact that steroids up‐regulate constitutive IL‐10 production by selectively triggering activation signals on monocytes.