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Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation.

Otterdal K, Haukeland JW, Yndestad A, Dahl TB, Holm S, Segers FM, Gladhaug IP, Konopski Z, Damås JK, Halvorsen B, Aukrust P - Clin Transl Gastroenterol (2015)

Bottom Line: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism.The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes.We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction.

View Article: PubMed Central - PubMed

Affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

ABSTRACT

Objectives: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD).

Methods: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR.

Results: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes.

Conclusion: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression.

No MeSH data available.


Related in: MedlinePlus

Impact of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) on the expression of interleukin-8 (IL-8) in Huh7 (human hepatoma cell line) hepatocytes. Effect of recombinant human LIGHT (ng/ml) on the expression of IL-8 in Huh7 hepatocytes after (a and b) 2 h and (c and d) 8 h stimulation. Left panels show mRNA levels of IL-8 from cell lysates, as assessed by real-time reverse transcription-PCR (RT-PCR), in relation to the control gene β-actin, and right panels show protein levels of IL-8 measured in the supernatant from cells by enzyme immunoassay. Data are given as mean±s.e.m., n=6. *P=0.06, *P<0.05, **P<0.01, and ****P<0.0001 vs. US (unstimulated).
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fig3: Impact of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) on the expression of interleukin-8 (IL-8) in Huh7 (human hepatoma cell line) hepatocytes. Effect of recombinant human LIGHT (ng/ml) on the expression of IL-8 in Huh7 hepatocytes after (a and b) 2 h and (c and d) 8 h stimulation. Left panels show mRNA levels of IL-8 from cell lysates, as assessed by real-time reverse transcription-PCR (RT-PCR), in relation to the control gene β-actin, and right panels show protein levels of IL-8 measured in the supernatant from cells by enzyme immunoassay. Data are given as mean±s.e.m., n=6. *P=0.06, *P<0.05, **P<0.01, and ****P<0.0001 vs. US (unstimulated).

Mentions: Hepatic inflammation is an important feature of NAFLD-related disease. To elucidate any potential pathogenic role of LIGHT in NAFLD, we next examined the ability of LIGHT to promote the production and release of prototypical inflammatory cytokines in Huh7 hepatocytes. Whereas LIGHT had no effect on the release of IL-6, TNFα, and monocyte chemoattractant protein-1, it markedly enhanced the IL-8 response in a time- and dose-dependent manner (Figure 3) both on protein and mRNA level.


Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation.

Otterdal K, Haukeland JW, Yndestad A, Dahl TB, Holm S, Segers FM, Gladhaug IP, Konopski Z, Damås JK, Halvorsen B, Aukrust P - Clin Transl Gastroenterol (2015)

Impact of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) on the expression of interleukin-8 (IL-8) in Huh7 (human hepatoma cell line) hepatocytes. Effect of recombinant human LIGHT (ng/ml) on the expression of IL-8 in Huh7 hepatocytes after (a and b) 2 h and (c and d) 8 h stimulation. Left panels show mRNA levels of IL-8 from cell lysates, as assessed by real-time reverse transcription-PCR (RT-PCR), in relation to the control gene β-actin, and right panels show protein levels of IL-8 measured in the supernatant from cells by enzyme immunoassay. Data are given as mean±s.e.m., n=6. *P=0.06, *P<0.05, **P<0.01, and ****P<0.0001 vs. US (unstimulated).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4816254&req=5

fig3: Impact of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) on the expression of interleukin-8 (IL-8) in Huh7 (human hepatoma cell line) hepatocytes. Effect of recombinant human LIGHT (ng/ml) on the expression of IL-8 in Huh7 hepatocytes after (a and b) 2 h and (c and d) 8 h stimulation. Left panels show mRNA levels of IL-8 from cell lysates, as assessed by real-time reverse transcription-PCR (RT-PCR), in relation to the control gene β-actin, and right panels show protein levels of IL-8 measured in the supernatant from cells by enzyme immunoassay. Data are given as mean±s.e.m., n=6. *P=0.06, *P<0.05, **P<0.01, and ****P<0.0001 vs. US (unstimulated).
Mentions: Hepatic inflammation is an important feature of NAFLD-related disease. To elucidate any potential pathogenic role of LIGHT in NAFLD, we next examined the ability of LIGHT to promote the production and release of prototypical inflammatory cytokines in Huh7 hepatocytes. Whereas LIGHT had no effect on the release of IL-6, TNFα, and monocyte chemoattractant protein-1, it markedly enhanced the IL-8 response in a time- and dose-dependent manner (Figure 3) both on protein and mRNA level.

Bottom Line: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism.The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes.We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction.

View Article: PubMed Central - PubMed

Affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

ABSTRACT

Objectives: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD).

Methods: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR.

Results: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes.

Conclusion: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression.

No MeSH data available.


Related in: MedlinePlus