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Regulation of stellate cell proliferation by lipopolysaccharide: Role of endogenous nitric oxide
Author(s) -
KAWADA NORIFUMI,
SEKI SHUICHI,
KUROKI TETSUO,
INOUE MASAYASU
Publication year - 1998
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.1998.13.s1.6
Subject(s) - lipopolysaccharide , nitric oxide , hepatic stellate cell , dna synthesis , cyclic guanosine monophosphate , endogeny , nitric oxide synthase , cell growth , cell culture , guanosine , thymidine , microbiology and biotechnology , cytokine , medicine , biology , endocrinology , biochemistry , dna , genetics
We studied the effect of lipopolysaccharide (LPS) on the proliferation of culture‐stimulated rat stellate cells. DNA synthesis as determined by [ 3 H]‐thymidine incorporation was significantly suppressed by up to 52% compared with the control culture in the presence of LPS (> 5 ng/mL). Such an inhibitory effect of LPS was dramatically augmented in the presence of interferon‐γ (IFNγ). Lipopolysaccharide alone or in combination with IFNγ activated transcription factors AP‐1 and NF‐κB, and elicited nitric oxide (NO) production by stellate cells by inducing NO synthase. Inhibition of NO production by the addition of L‐arginine antagonists to the culture, partially cancelled such an inhibitory effect of LPS and/or IFNγ on DNA synthesis without affecting the activation of AP‐1 and NF‐κB and the NO synthase level. The cellular level of cyclic guanosine monophosphate (cGMP) increased in response to LPS and IFNγ, and dibutyryl cGMP or 8‐bromo‐cGMP inhibited the incorporation of [ 3 H]‐thymidine in a dose‐dependent manner. These results indicate that LPS is potent in modulating stellate cell proliferation by some NO‐ and cGMP‐dependent mechanism.