Interleukin–10 Expression and Function in Experimental Murine Liver Inflammation and Fibrosis

Thompson, Kerry C.; Maltby, Julia; Fallowfield, Jonathan; McAulay, M.; Millward-Sadler, Harry; Sheron, Nick

doi:10.1002/hep.510280620

Cited by 226 publications

(147 citation statements)

References 39 publications

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“…In contrast, mRNA levels of the anti-inflammatory cytokine, IL-10, were significantly reduced in the fatty liver. 6 In normal livers, double insults with alcohol and LPS attenuated LPS-induced proinflammatory cytokine mRNA induction of IL-12, IL-1␤ and IL-6 (Fig. 2B).…”

Section: Opposite Regulation Of Serum Tnf-␣ and Il-6 Levels In Mice Wmentioning

confidence: 83%

“…It is known that disruption of the anti-inflammatory interleukin (IL) 10 gene potentiates TNF-␣-induced liver injury. 6 Previous studies have demonstrated increased susceptibility of the fatty liver to lipopolysaccharide (LPS)-induced injury. 1,3 LPS triggers both pro-and anti-inflammatory pathways and, depending on their balance, results in a self-limiting, transient, or prolonged inflammatory activation.…”

mentioning

confidence: 99%

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Diverse regulation of NF-κB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver

et al. 2004

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Fatty liver is highly sensitive to inflammatory activation. Peroxisome proliferator-activated receptors (PPAR) have anti-inflammatory effects and regulate lipid metabolism in the fatty liver. We hypothesized that fatty liver leads to endotoxin sensitivity through an imbalance between pro-and anti-inflammatory signals. Leptin-deficient, ob/ob mice and their lean littermates were challenged with single or double insults and pro-and anti-inflammatory pathways were tested on cytokine production and activation of nuclear regulatory factors NF-B and peroxisome proliferator receptor element (PPRE). Ob/ob mice produced significantly higher serum tumor necrosis factor ␣ (TNF-␣) and interleukin (

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Section: Opposite Regulation Of Serum Tnf-␣ and Il-6 Levels In Mice Wmentioning

confidence: 83%

mentioning

confidence: 99%

Diverse regulation of NF-κB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver

et al. 2004

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“…Thus, the protease-mediated release of IL-10 in inflammatory sites may represent a protective mechanism designed to promote resolution of inflammation by enhancing neutrophil apoptosis. Certainly, in its absence, inflammation is more severe in a number of models (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Apoptotic Versus Lysed Cells on Macrophage Production of Cytokines: Role of Proteases

Fadok

Bratton

Guthrie

et al. 2001

The Journal of Immunology

338

284

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Granulocytes undergoing apoptosis are recognized and removed by phagocytes before their lysis. The release of their formidable arsenal of proteases and other toxic intracellular contents into tissues can create significant damage, prolonging the inflammatory response. Binding and/or uptake of apoptotic cells by macrophages inhibits release of proinflammatory cytokines by mechanisms that involve anti-inflammatory mediators, including TGF-β. To model the direct effects of necrotic cells on macrophage cytokine production, we added lysed or apoptotic neutrophils and lymphocytes to mouse and human macrophages in the absence of serum to avoid complement activation. The results confirmed the ability of lysed neutrophils, but not lymphocytes, to significantly stimulate production of macrophage-inflammatory protein 2 or IL-8, TNF-α, and IL-10. Concomitantly, induction of TGF-β1 by lysed neutrophils was significantly lower than that observed for apoptotic cells. The addition of selected serine protease inhibitors and anti-human elastase Ab markedly reduced the proinflammatory effects, the lysed neutrophils then behaving as an anti-inflammatory stimulus similar to intact apoptotic cells. Separation of lysed neutrophils into membrane and soluble fractions showed that the neutrophil membranes behaved like apoptotic cells. Thus, the cytokine response seen when macrophages were exposed to lysed neutrophils was largely due to liberated proteases. Therefore, we suggest that anti-inflammatory signals can be given by PtdSer-containing cell membranes, whether from early apoptotic, late apoptotic, or lysed cells, but can be overcome by proteases liberated during lysis. Therefore, the outcome of an inflammatory reaction and the potential immunogenicity of Ags within the damaged cell will be determined by which signals predominate.

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“…At least 10 fields were scored per liver section to obtain the mean value. The scoring system for CCl 4 chronic changes of hepatic inflammation, balloon degeneration and fibrosis were evaluated according to a score proposed by Thompson [23] Alcohol dehydrogenase (ADH) activity in liver tissues A 10% liver homogenate was used for the determination of the levels of ADH activities in liver tissues. ADH activity was detected colorimetrically with UV-visible spectrophotometer using commercial kits (Nanjing Jian Cheng Bioengineering Institute, Nanjing, China) according to the manufacturer's protocol.…”

Section: Histopathological Examination and Immunohistochemistrymentioning

confidence: 99%

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

Gao

Chu

et al. 2014

Acta Pharmacol Sin

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Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol-and CCl 4 -induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl 4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol-and CCl 4 -treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl 4 -induced cell proliferation, reversed CCl 4-induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl 4 -treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol-and CCl 4 -induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes.

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Interleukin–10 Expression and Function in Experimental Murine Liver Inflammation and Fibrosis

Cited by 226 publications

References 39 publications

Diverse regulation of NF-κB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver

Diverse regulation of NF-κB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver

Differential Effects of Apoptotic Versus Lysed Cells on Macrophage Production of Cytokines: Role of Proteases

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

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