TY - JOUR
T1 - Detection of serum nitrite and nitrate in primary biliary cirrhosis
T2 - Possible role of nitric oxide in bile duct injury
AU - Hokari, Atsushi
AU - Zeniya, Mikio
AU - Esumi, Hiroyasu
AU - Kawabe, Tomonobu
AU - Gershwin, M. Eric
AU - Toda, Gotaro
PY - 2002
Y1 - 2002
N2 - Background: The role of nitric oxide synthase (NOS) in autoimmune disease is gaining increased attention because of the relationships between NOS activity and T-lymphocyte subpopulations and, in particular, the influence of NO on cytokine production by Th1 versus Th2 cells. In addition, there is evidence that both the liver and infiltrating hepatic T cells have inducible NOS-2 activity. Methods: We studied serum levels of nitrite (NO2
-) and nitrate (NO3
-) in groups of patients with liver disease secondary to hepatitis B, hepatitis C, autoimmune hepatitis and primary biliary cirrhosis (PBC). Simultaneously, in a nested subpopulation, we studied the liver expression of NOS-2. Results: Interestingly, there was a significant elevation both of nitrite and of nitrate in patients with PBC but not other liver diseases. Despite such increments, there was no correlation of the levels of nitrite and nitrate with sera levels of tumor necrosis factor-α, interferon-γ, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, platelet count, IgG, IgM, antimitochondrial antibodies or prothrombin time. These data were extended by demonstrating the expression of NOS-2 by immunohistochemistry in 13/14 patients with PBC, including in 9/14 patient hepatocyte populations and 4/14 bile duct cells. In contrast, NOS-2 expression was noted in hepatitis B and hepatitis C, but only found within mononuclear cells. Conclusion: Our data suggest that NO produced through NOS-2 may play a role in the pathogenesis of bile duct injury in some PBC patients.
AB - Background: The role of nitric oxide synthase (NOS) in autoimmune disease is gaining increased attention because of the relationships between NOS activity and T-lymphocyte subpopulations and, in particular, the influence of NO on cytokine production by Th1 versus Th2 cells. In addition, there is evidence that both the liver and infiltrating hepatic T cells have inducible NOS-2 activity. Methods: We studied serum levels of nitrite (NO2
-) and nitrate (NO3
-) in groups of patients with liver disease secondary to hepatitis B, hepatitis C, autoimmune hepatitis and primary biliary cirrhosis (PBC). Simultaneously, in a nested subpopulation, we studied the liver expression of NOS-2. Results: Interestingly, there was a significant elevation both of nitrite and of nitrate in patients with PBC but not other liver diseases. Despite such increments, there was no correlation of the levels of nitrite and nitrate with sera levels of tumor necrosis factor-α, interferon-γ, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, platelet count, IgG, IgM, antimitochondrial antibodies or prothrombin time. These data were extended by demonstrating the expression of NOS-2 by immunohistochemistry in 13/14 patients with PBC, including in 9/14 patient hepatocyte populations and 4/14 bile duct cells. In contrast, NOS-2 expression was noted in hepatitis B and hepatitis C, but only found within mononuclear cells. Conclusion: Our data suggest that NO produced through NOS-2 may play a role in the pathogenesis of bile duct injury in some PBC patients.
KW - Nitrate
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Nitrite
KW - Primary biliary cirrhosis
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U2 - 10.1046/j.1440-1746.2002.02689.x
DO - 10.1046/j.1440-1746.2002.02689.x
M3 - Article
C2 - 11982702
AN - SCOPUS:0036097310
VL - 17
SP - 308
EP - 315
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
SN - 0815-9319
IS - 3
ER -