Abstract
Background. The current study evaluated whether biliary tract obstruction stimulates inducible
nitric oxide synthase (iNOS) protein expression in the liver and analyzed the implication
of lymphomononuclear cells and interleukin-4 (IL-4). Methods. Male Wistar rats were used. Bile flow interruption was achieved by a complete division
of the extrapancreatic common bile duct. iNOS expression was determined by both the
Western blot technique and immunohistochemistry. Results. iNOS protein was markedly expressed in the liver 7 days after bile duct obstruction.
Treatment with thymostimulin (TP-1), a partially purified thymic extract, reduced
the intensity of the expression of iNOS protein in the liver after bile duct ligation.
Recent data have suggested that IL-4 attenuates iNOS protein expression. We then analyzed
the involvement of this anti-inflammatory cytokine on the modulation of iNOS expression
in the liver. The liver from rats that underwent bile duct ligation (BDL) showed a
lower content of IL-4 than that of sham-operated (SO) rats. TP-1 treatment increased
the content of IL-4 in the liver. Liver slices incubated in vitro with Escherichia
coli lipopolysaccharide (LPS, 10 μg/mL) stimulated the expression of iNOS protein.
The level of LPS-induced iNOS expression was reduced by lymphomononuclear cells obtained
from sham-operated animals. However, lymphomononuclear cells isolated from BDL rats
potentiated the induction of iNOS expression by LPS-stimulated liver. However, lymphomononuclear
cells from TP-1—treated BDL rats failed to modify LPS-stimulated iNOS expression.
The different effect of lymphomononuclear cells on the modulation of iNOS expression
in the liver was associated with their ability to generate IL-4. Conclusions. The liver of jaundiced rats markedly expressed iNOS protein, which was associated
to modifications in the content of IL-4 in the liver. Furthermore, lymphomononuclear
cells modulate iNOS protein expression in the liver by a mechanism in which IL-4 is
involved. (Surgery 2001;129:255-66.)
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Article info
Publication history
Accepted:
July 22,
2000
Footnotes
☆Supported by grants from Fondo de Investigaciones Sanitarias de la Seguridad Social (98/0648) and Comunidad Autónoma de Madrid (08.2/0003/98).
☆☆Surgery 2001;129:255-66.
★M. M. Arriero, J. A. Rodríguez-Feo, S. Velasco, and M. García-Durán are fellows of the Fundación Conchita Rábago de Jiménez Díaz.
★★Reprint requests: Ángel Celdrán, Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
