Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis.
We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 +/- 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1beta was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.
Toda
K
K
Biomedical Laboratory, Kitasato Institute Hospital, Tokyo, Japan.
Kumagai
N
N
Tsuchimoto
K
K
Inagaki
H
H
Suzuki
T
T
Oishi
T
T
Atsukawa
K
K
Saito
H
H
Morizane
T
T
Hibi
T
T
Ishii
H
H
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D015850:Interleukin-6