Article
Upregulation by glucocorticoids of responses to eosinopoietic cytokines in bone-marrow from normal and allergic mice
Registro en:
ELSAS, Maria Ignez C. Gaspar et al. Upregulation by glucocorticoids of responses to eosinopoietic cytokines in bone-marrow from normal and allergic mice. Br. j. clin. pharmacol., London, v. 129, n. 8, p. 1543-1552, apr. 2000.
1365-2125
Autor
Elsas, Maria Ignez Capella Gaspar
Maximiniano, Elisabeth S.
Joseph, Danielle
Alves, Letícia
Topilko, Andrzej
Vargaftig, B. Boris
Xavier-Elsas, Pedro Paulo
Resumen
PAPES/FIOCRUZ, FINEP, CNPq/RHAE,INSERM/FIOCRUZ, CAPES-COFECUB Institut Pasteur/INSERM Since the production of eosinopoietic cytokines (GM-CSF, IL-3, IL-5) is inhibited by glucocorticoids, while responsiveness to these cytokines is enhanced in bone-marrow of allergic mice, we studied the ability of glucocorticoids to modulate murine bone-marrow eosinopoiesis. Progenitor (semi-solid) and/or precursor (liquid) cultures were established from bone-marrow of: (a) normal mice; (b) ovalbumin-sensitized and challenged mice or (c) dexamethasone (1-5 mg kg(-1)) injected mice. Cultures were established with GM-CSF (2 ng ml(-1)) or IL-5 (1 ng ml(-1)), respectively, alone or associated with dexamethasone, hydrocortisone or corticosterone. Total myeloid colony numbers, frequency and size of eosinophil colonies, and numbers of eosinophil-peroxidase-positive cells were determined at day 7. In BALB/c mice, dexamethasone (10(-7) M) increased GM-CSF-stimulated myeloid colony formation (P = 0.01), as well as the frequency (P=0.01) and size (P<0.01) of eosinophil colonies. Dexamethasone (10(-7) M) alone had no effect. Dexamethasone (10(-7)-10(-10) M) increased (P<0.002) eosinophil precursor responses to IL-5. Potentiation by dexamethasone was still detectable: (a) on low density, immature, nonadherent BALB/c bone-marrow cells, (b) on bone-marrow from other strains, and (c) on cells from allergic mice. Hydrocortisone and corticosterone had similar effects. Dexamethasone administered in vivo, 24 h before bone-marrow harvest, increased subsequent progenitor responses to GM-CSF (P = 0.001) and precursor responses to IL-5 (P<0.001). These effects were blocked by RU 486 (20 mg kg(-1), orally, 2 h before dexamethasone, or added in vitro at 10 microM, P<0.001). Glucocorticoids, acting in vivo or in vitro, through glucocorticoid receptors, enhance bone-marrow eosinopoiesis in naïve and allergic mice.