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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

Levels of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in patients and controls. Serum levels of LIGHT were assessed by enzyme immunoassay, in healthy control subjects (n=16), patients with simple steatosis (n=34), and patients with nonalcoholic steatohepatitis (NASH) (n=32). Horizontal lines indicate median values.
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fig1: Levels of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in patients and controls. Serum levels of LIGHT were assessed by enzyme immunoassay, in healthy control subjects (n=16), patients with simple steatosis (n=34), and patients with nonalcoholic steatohepatitis (NASH) (n=32). Horizontal lines indicate median values.

Mentions: Patients with NAFLD (n=66) had significantly raised serum levels of LIGHT as compared with healthy controls (n=16) (mean (s.d.): 79.1 (53.49) vs. 26.4 (24.6) pg/ml, P<0.001), with no significant difference between simple steatosis (n=34) and NASH (n=32) (mean (s.d.): 85.3 (55.6) vs. 70.4 (50.8) pg/ml, P=0.26), simple steatosis, and NASH, respectively) (Figure 1). After adjustment for sex, BMI, and age, the diagnosis of NAFLD was still a significant predictor of LIGHT (P<0.001; Table 2). Moreover, within the NAFLD goup, there was no difference in LIGHT levels between those who met (n=47) and those who did not meet (n=19) the criteria for metabolic syndrome (mean (s.d.): 79.1 (55.1) vs. 75.5 (50.5) pg/ml, P=0.80). Also, there was no difference in serum levels of LIGHT when comparing those with and without fibrosis (data not shown).


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)

Levels of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in patients and controls. Serum levels of LIGHT were assessed by enzyme immunoassay, in healthy control subjects (n=16), patients with simple steatosis (n=34), and patients with nonalcoholic steatohepatitis (NASH) (n=32). Horizontal lines indicate median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Levels of LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in patients and controls. Serum levels of LIGHT were assessed by enzyme immunoassay, in healthy control subjects (n=16), patients with simple steatosis (n=34), and patients with nonalcoholic steatohepatitis (NASH) (n=32). Horizontal lines indicate median values.
Mentions: Patients with NAFLD (n=66) had significantly raised serum levels of LIGHT as compared with healthy controls (n=16) (mean (s.d.): 79.1 (53.49) vs. 26.4 (24.6) pg/ml, P<0.001), with no significant difference between simple steatosis (n=34) and NASH (n=32) (mean (s.d.): 85.3 (55.6) vs. 70.4 (50.8) pg/ml, P=0.26), simple steatosis, and NASH, respectively) (Figure 1). After adjustment for sex, BMI, and age, the diagnosis of NAFLD was still a significant predictor of LIGHT (P<0.001; Table 2). Moreover, within the NAFLD goup, there was no difference in LIGHT levels between those who met (n=47) and those who did not meet (n=19) the criteria for metabolic syndrome (mean (s.d.): 79.1 (55.1) vs. 75.5 (50.5) pg/ml, P=0.80). Also, there was no difference in serum levels of LIGHT when comparing those with and without fibrosis (data not shown).

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