Changes of serum cytokines and expression of inducible nitric oxide synthase mRNA by Kupffer cells after relief from obstructive jaundice in rats

Meng, Ying; Gong, Yan; Dou, Yan; Li, Wen

doi:10.1111/j.1440-1746.2008.05746.x

Cited by 14 publications

(14 citation statements)

References 32 publications

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“…Therefore, our results suggest that induction of iNOS in HSC could play a role in eliminating these cells by apoptosis, contributing to the termination of the fibrogenic response. There are contradictory results regarding to the nature of the effect of NO released in the liver by different cells including endothelial cells, macrophages, hepatocytes, and Kupffer cells (Aram et al, 2008;Meng et al, 2009). However, induction of apoptosis by endogenous NO production mediated by caspase-3 activation has been also described in other cell types (Choi et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Fibronectin Peptides as Potential Regulators of Hepatic Fibrosis Through Apoptosis of Hepatic Stellate Cells

Mòdol

Brice

Galarreta

et al. 2014

Journal Cellular Physiology

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The turnover of extracellular matrix (ECM) components can generate signals that regulate several cellular functions such as proliferation, differentiation, and apoptosis. During liver injury, matrix metalloproteases (MMPs) production is enhanced and increased levels of peptides derived from extracellular matrix proteins can be generated. Synthetic peptides with sequences present in extracellular matrix proteins were previously found to induce both stimulating and apoptotic effects on several cell types including the inflammatory cells monocytes/macrophages. Therefore, in inflammatory liver diseases, locally accumulated peptides could be also important in regulating hepatic fibrosis by inducing apoptosis of hepatic stellate cells (HSC), the primary cellular source of extracellular matrix components. Here, we describe the apoptotic effect of fibronectin peptides on the cell line of human hepatic stellate cells LX-2 based on oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion, and accumulation of Bax protein. We also found that these peptides trigger the activation of Src kinase, which in turn mediated the increase of JNK and p38 activities. By the use of specific inhibitors we demonstrated the involvement of Src, JNK, and p38 in apoptosis induced by fibronectin peptides on HSC. Moreover, fibronectin peptides increased iNOS expression in human HSC, and specific inhibition of iNOS significantly reduced the sustained activity of JNK and the programmed cell death caused by these peptides. Finally, the possible regulatory effect of fibronectin peptides in liver fibrosis was further supported by the ability of these peptides to induce metalloprotease-9 (MMP-9) expression in human monocytes.

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Section: Discussionmentioning

confidence: 99%

Fibronectin Peptides as Potential Regulators of Hepatic Fibrosis Through Apoptosis of Hepatic Stellate Cells

Mòdol

Brice

Galarreta

et al. 2014

Journal Cellular Physiology

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“…In addition to the plasma TNF‐α level, ILs were considered to be positively correlated with inflammation in liver injury. Among various ILs, IL‐6 was shown to be increased in rats with obstructive jaundice, 31 and validated as an important contributor to minimal hepatic encephalopathy 32 . Besides, the association between IL‐1 and liver injury was verified in CCl 4 ‐treated rats 17 .…”

Section: Discussionmentioning

confidence: 92%

Lack of therapeutic effects of gabexate mesilate on the hepatic encephalopathy in rats with acute and chronic hepatic failure

Hsu

Lee

Huo

et al. 2010

J of Gastro and Hepatol

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“…The results of the present study indicate that cytokine responses in patients with malignant OJ were impaired to a greater extent when compared with those with benign OJ. The capacity of Kupffer cells to clear LPS may be impaired in the presence of OJ [ 9 , 37 , 38 ], thus exposing immune cells to higher concentrations of LPS and for prolonged periods. This prolonged exposure to LPS with impaired Kupffer cell function may be one possible mechanism for the differences observed between benign and malignant groups.…”

Section: Discussionmentioning

confidence: 99%

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography

et al. 2016

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This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1β: 2678 compared with 4631 pg/ml, P=0.04 and IL-6: 3442 compared with 6157 pg/ml, P=0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1β: 2025 compared with 3332 pg/ml, P=0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1β: 2150 compared with 2520 pg/ml, P=0.03 and IL-6: 2488 compared with 3250 pg/ml, P=0.01). Occludin expression (85 compared with 95%, P=0.004) and mean duodenal villus height (334 compared with 404 μm, P=0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P=0.04) and CD86 (P=0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage.

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Changes of serum cytokines and expression of inducible nitric oxide synthase mRNA by Kupffer cells after relief from obstructive jaundice in rats

Abstract: The levels of serum endotoxin, TNF-alpha and IL-6 and the expression of iNOS mRNA by Kupffer cells were increased in rats with obstructive jaundice. Internal biliary drainage could entirely reverse the changes, but external drainage only partially did.

Cited by 14 publications

References 32 publications

Fibronectin Peptides as Potential Regulators of Hepatic Fibrosis Through Apoptosis of Hepatic Stellate Cells

Fibronectin Peptides as Potential Regulators of Hepatic Fibrosis Through Apoptosis of Hepatic Stellate Cells

Lack of therapeutic effects of gabexate mesilate on the hepatic encephalopathy in rats with acute and chronic hepatic failure

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography

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