Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
19/10/2012
19/10/2012
2010
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Resumo |
IL-13 and eotaxin play important, inter-related roles in asthma models. In the lungs, CysLT, produced by the 5-LO-LTC4S pathway, mediate some local responses to IL-13 and eotaxin; in bone marrow, CysLT enhance IL-5-dependent eosinophil differentiation. We examined the effects of IL-13 and eotaxin on eosinophil differentiation. Semi-solid or liquid cultures were established from murine bone marrow with GM-CSF or IL-5, respectively, and the effects of IL-13, eotaxin, or CysLT on eosinophil colony formation and on eosinophil differentiation in liquid culture were evaluated, in the absence or presence of: a) the 5-LO inhibitor zileuton, the FLAP inhibitor MK886, or the CysLT1R antagonists, montelukast and MK571; b) mutations that inactivate 5-LO, LTC4S, or CysLT1R; and c) neutralizing mAb against eotaxin and its CCR3 receptor. Both cytokines enhanced GM-CSF-dependent eosinophil colony formation and IL-5-stimulated eosinophil differentiation. Although IL-13 did not induce eotaxin production, its effects were abolished by anti-eotaxin and anti-CCR3 antibodies, suggesting up-regulation by IL-13 of responses to endogenous eotaxin. Anti-CCR3 blocked eotaxin completely. The effects of both cytokines were prevented by zileuton, MK886, montelukast, and MK571, as well as by inactivation of the genes coding for 5-LO, LTC4S, and CysLT1R. In the absence of either cytokine, these treatments or mutations had no effect. These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals. J. Leukoc. Biol. 87: 885-893; 2010. National Institutes of Health (NIH)[HL082695] CNPq[474979/2004-0] CNPq[471176/2007-9] CNPq[478253/2008-7] Research Productivity Fellowships FAPERJ[E-26/110.188/2008] FIOCRUZ. Expert |
Identificador |
JOURNAL OF LEUKOCYTE BIOLOGY, v.87, n.5, p.885-893, 2010 0741-5400 http://producao.usp.br/handle/BDPI/24332 10.1189/jlb.1108709 |
Idioma(s) |
eng |
Publicador |
FEDERATION AMER SOC EXP BIOL |
Relação |
Journal of Leukocyte Biology |
Direitos |
restrictedAccess Copyright FEDERATION AMER SOC EXP BIOL |
Palavras-Chave | #secreted regulatory products #lipid mediators #signaling cascade #GENE DISRUPTION REVEALS #VASCULAR-PERMEABILITY #INFLAMMATORY RESPONSES #EXPERIMENTAL ASTHMA #MICE #IL-13 #LUNG #PROGENITORS #HYPERREACTIVITY #MEDIATE #Cell Biology #Hematology #Immunology |
Tipo |
article original article publishedVersion |