Upregulation by glucocorticoids of responses to eosinopoietic cytokines in bone-marrow from normal and allergic mice

Submitted by Luis Guilherme Macena ([email protected]) on 2013-03-11T14:29:27Z No. of bitstreams: 1 Upregulation by glucocorticoids of responses to eosinopoietic.pdf: 420642 bytes, checksum: 9b1d31865e9436398981bc9a3badc3ca (MD5)Made available in DSpace on 2013-03-11T14:29:27Z (GMT). No. of bitstreams: 1 Upregulation by glucocorticoids of responses to eosinopoietic.pdf: 420642 bytes, checksum: 9b1d31865e9436398981bc9a3badc3ca (MD5) Previous issue date: 2000PAPES/FIOCRUZ, FINEP, CNPq/RHAE,INSERM/FIOCRUZ, CAPES-COFECUB Institut Pasteur/INSERMFundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Pesquisa. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilINSERM. Unité Associeé Institut Pasteur. Uniteé de Pharmacologie Cellulaire. Paris, FranceUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilInstitut Pasteur. Station Centrale de Microscopie Électronique. Paris, FranceINSERM. Unité Associeé Institut Pasteur. Uniteé de Pharmacologie Cellulaire. Paris, FranceUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilSince 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

Intimate adhesion of Neisseria meningitidis to human epithelial cells is under the control of the crgA gene, a novel LysR-type transcriptional regulator

PilC1, a pilus-associated protein in Neisseria menin– gitidis, is a key element in initial meningococcal adhesion to target cells. A promoter element (CREN, contact regulatory element of Neisseria) is responsible for the transient induction of this gene upon cell contact. crgA (contact-regulated gene A) encodes a transcriptional regulator whose expression is also induced upon cell contact from a promoter region similar to the CREN of pilC1. CrgA shows significant sequence homologies to LysR-type transcriptional regulators. Its inactivation in meningococci provokes a dramatic reduction in bacterial adhesion to epithelial cells. Moreover, this mutant is unable to undergo intimate adhesion to epithelial cells or to provoke effacing of microvilli on infected cells. Purified CrgA is able to bind to pilC1 and crgA promoters, and CrgA seems to repress the expression of pilC1 and crgA. Our results support a dynamic model of bacteria–cell interaction involving a network of regulators acting in cascade. CrgA could be an intermediate regulator in such a network