Expression of inducible nitric oxide synthase in the liver of bile duct-ligated Wistar rats with modulation by lymphomononuclear cells

Background. The current study evaluated whether biliary tract obstruction s timulates inducible nitric oxide synthase (iNOS) protein expression in the liver and analyzed the implication of lymphomononuclear cells and interleuk in-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 expressi on was determined by both the Western blot technique and immunohistochemist ry. Results. iNOS protein was markedly expressed in the liver 7 days after bile duct obstruction. Treatment with thymostimulin (TP-I), a partially purifie d 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 a ttenuates iNOS protein expression. We then analyzed the involvement of this anti-inflammatory cytokine on the modulation of iNOS expression in the liv er. The liver from rats that underwent bile duct ligation (BDL) showed a lo wer content of IL-4 than that of sham-operated (SO) rats. TP-I treatment in creased the content of IL-4 in the liver Liver slices incubated in vitro wi th Escherichia coli lipopolysaccharide (LPS, 10 mug/mL) stimulated the expr ession of iNOS protein. The level of LPS-induced iNOS expression was reduce d by lymphomononuclear cells obtained from sham-operated animals. However l ymphomononuclear cells isolated from BDL rats potentiated the induction of iNOS expression by LPS-stimulated liver However lymphomononuclear cells fro m TP-1-treated BDL rats failed to modify LPS-stimulated iNOS expression. Th e different effect of lymphomononuclear cells on the modulation of iNOS exp ression in the liver was associated with their ability to generate IL-4. Conclusions. The liver of jaundiced rats markedly expressed iNOS protein, w hich was associated to modifications in the content of IL-4 in the liver Fu rthermore, lymphomononuclear cells modulate iNOS protein expression in the liver by a mechanism in which IL-4 is involved.