Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow


Autoria(s): QUETO, Tulio; GASPAR-ELSAS, Maria I.; MASID-DE-BRITO, Daniela; VASCONCELOS, Zilton F. M.; FERRARIS, Fausto K.; PENIDO, Carmen; CUNHA, Fernando Q.; KANAOKA, Yoshihide; LAM, Bing K.; XAVIER-ELSAS, Pedro
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2010

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

http://dx.doi.org/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