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Noviembre 2005
Dr. Juan Rodríguez-Tafur D.Profesor Asociado de Inmunología y Farmacología
Facultad de MedicinaUniversidad Nacional Mayor de San Marcos. Lima (Perú)
Secretario de la Sociedad Peruana de Alergía e Inmunología
www.alergomurcia.com
The New England Journal of Medicine
Vol. 336(15) Apr 10, 1997 pp 1066-1071
Mechanisms of Disease: Nuclear Factor-(kappa)B --a Pivotal Transcription Factor in ChronicInflammatory Diseases. Barnes, Peter J.; Karin, Michael.
The New England Journal of Medicine
Vol. 336(15) Apr 10, 1997 pp 1066-1071
Mechanisms of Disease: Nuclear Factor-(kappa)B --a Pivotal Transcription Factor in ChronicInflammatory Diseases. Barnes, Peter J.; Karin, Michael.
Noviembre 2005 www.alergomurcia.com
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p65p50IkB
p65p50IkB
p65p50núcleo
señalP
quinasaIkB
P
quinasa
ComplejoNF-kB
Noviembre 2005 www.alergomurcia.com
Noviembre 2005 www.alergomurcia.com
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Noviembre 2005 www.alergomurcia.com
© 2003 By Default!
A Free sample background from www.powerpointbackgrounds.com
Slide 6
Sustancia PSustancia P
C5aC5a
OpiáceosOpiáceos
ALERGENO
PBM eosinofIlicaPBM eosinofIlica
FcεRIFcεRIIgE
NO INMUNOLOGICOINMUNOLOGICO
Toll-like receptorToll-like receptor
Productos bacterias, virusProductos bacterias, virus
Noviembre 2005 www.alergomurcia.com
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Noviembre 2005
Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):380-3.Hypothetical mechanisms of action of an H1-antihistamine in asthma.
Rihoux JP, Michel L, Arnold R, Koning WUCB SA, Chemin du Foriest B-1420 Braine-l'Alleud, Belgium.
Some recent clinical studies carried out with the potent H1-antihistamine cetirizine (CTZ) suggest that this drug could be useful for the treatment of mild to moderate asthma and even for the prevention of the disease. Besides a potent antagonism of H1-receptors at bronchial level, this drug was also shown to exert a large series of anti-inflammatory effects in in vitro, ex vivo and in vivo pharmacological models and also in clinical situations in atopic subjects. All the data collected up to now suggest the possible existence in the molecule of a central key mechanism of action on resident cells especially involved in cell trafficking and bronchial inflammation, i.e a down-regulating effect on the nuclear factorKappaB (NFkappaB). This hypothesis was tested on human endothelial cells and a human epithelial pulmonary cell line using different experimental methods. The results showed that CTZ down-regulates the TNF-alpha-induced hyperactivation of NFKappaB in these two different resident cells at physiological concentrations.
Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):380-3.Hypothetical mechanisms of action of an H1-antihistamine in asthma.
Rihoux JP, Michel L, Arnold R, Koning WUCB SA, Chemin du Foriest B-1420 Braine-l'Alleud, Belgium.
Some recent clinical studies carried out with the potent H1-antihistamine cetirizine (CTZ) suggest that this drug could be useful for the treatment of mild to moderate asthma and even for the prevention of the disease. Besides a potent antagonism of H1-receptors at bronchial level, this drug was also shown to exert a large series of anti-inflammatory effects in in vitro, ex vivo and in vivo pharmacological models and also in clinical situations in atopic subjects. All the data collected up to now suggest the possible existence in the molecule of a central key mechanism of action on resident cells especially involved in cell trafficking and bronchial inflammation, i.e a down-regulating effect on the nuclear factorKappaB (NFkappaB). This hypothesis was tested on human endothelial cells and a human epithelial pulmonary cell line using different experimental methods. The results showed that CTZ down-regulates the TNF-alpha-induced hyperactivation of NFKappaB in these two different resident cells at physiological concentrations.
www.alergomurcia.com
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Noviembre 2005 www.alergomurcia.com
Noviembre 2005 www.alergomurcia.com
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0
2
4
6
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10
12
14
Dosis Requerida para Inhibir el 50% del NFkB
nano
Mol
es
DLDL CE
TIR
IZIN
AC
ET
IRIZ
INA
LO
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DIN
AL
OR
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FEX
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DIN
AFE
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FEN
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x 12x 14x 19xx 12x 14x 19x
0.67
8.1 9.3
13
Noviembre 2005 www.alergomurcia.com
J A
llerg
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01;1
08:2
21-8
J A
llerg
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linIm
mun
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01;1
08:2
21-8
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Noviembre 2005