Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease

Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuhiro Nouso, Atsuko Nakatsuka, Jun Wada, Kazuko Koike, Koji Miyahara, Hidenori Shiraha, Kazuhide Yamamoto, Hiroyuki Okada

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH. Methods: A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified. Results: One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-γ-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation. Conclusions: IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalHepatology International
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Fatty Liver
Disease Progression
Blood Proteins
Cytokines
Insulin Resistance
Toll-Like Receptor 2
Monocytes
Non-alcoholic Fatty Liver Disease
Messenger RNA
Liver
Proteins
Alcoholic Fatty Liver
Chemokine CXCL10
Insulin
Biopsy
Glucose
Cell Line
Interleukin-15
Toll-Like Receptors
Real-Time Polymerase Chain Reaction

Keywords

  • Insulin resistance, interferon-γ-inducible protein-10
  • Non-alcoholic fatty liver disease
  • Non-alcoholic steatohepatitis

ASJC Scopus subject areas

  • Hepatology

Cite this

Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease. / Wada, Nozomu; Takaki, Akinobu; Ikeda, Fusao; Yasunaka, Tetsuya; Onji, Masahiro; Nouso, Kazuhiro; Nakatsuka, Atsuko; Wada, Jun; Koike, Kazuko; Miyahara, Koji; Shiraha, Hidenori; Yamamoto, Kazuhide; Okada, Hiroyuki.

In: Hepatology International, Vol. 11, No. 1, 01.01.2017, p. 115-124.

Research output: Contribution to journalArticle

Wada, Nozomu ; Takaki, Akinobu ; Ikeda, Fusao ; Yasunaka, Tetsuya ; Onji, Masahiro ; Nouso, Kazuhiro ; Nakatsuka, Atsuko ; Wada, Jun ; Koike, Kazuko ; Miyahara, Koji ; Shiraha, Hidenori ; Yamamoto, Kazuhide ; Okada, Hiroyuki. / Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease. In: Hepatology International. 2017 ; Vol. 11, No. 1. pp. 115-124.
@article{e64be173d6cb4902bca5991289584c82,
title = "Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease",
abstract = "Background: The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH. Methods: A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified. Results: One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-γ-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90{\%}, with specificity of 50{\%}. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation. Conclusions: IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.",
keywords = "Insulin resistance, interferon-γ-inducible protein-10, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis",
author = "Nozomu Wada and Akinobu Takaki and Fusao Ikeda and Tetsuya Yasunaka and Masahiro Onji and Kazuhiro Nouso and Atsuko Nakatsuka and Jun Wada and Kazuko Koike and Koji Miyahara and Hidenori Shiraha and Kazuhide Yamamoto and Hiroyuki Okada",
year = "2017",
month = "1",
day = "1",
doi = "10.1007/s12072-016-9773-y",
language = "English",
volume = "11",
pages = "115--124",
journal = "Hepatology International",
issn = "1936-0533",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease

AU - Wada, Nozomu

AU - Takaki, Akinobu

AU - Ikeda, Fusao

AU - Yasunaka, Tetsuya

AU - Onji, Masahiro

AU - Nouso, Kazuhiro

AU - Nakatsuka, Atsuko

AU - Wada, Jun

AU - Koike, Kazuko

AU - Miyahara, Koji

AU - Shiraha, Hidenori

AU - Yamamoto, Kazuhide

AU - Okada, Hiroyuki

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH. Methods: A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified. Results: One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-γ-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation. Conclusions: IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.

AB - Background: The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH. Methods: A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified. Results: One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-γ-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation. Conclusions: IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.

KW - Insulin resistance, interferon-γ-inducible protein-10

KW - Non-alcoholic fatty liver disease

KW - Non-alcoholic steatohepatitis

UR - http://www.scopus.com/inward/record.url?scp=84994389315&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994389315&partnerID=8YFLogxK

U2 - 10.1007/s12072-016-9773-y

DO - 10.1007/s12072-016-9773-y

M3 - Article

C2 - 27826704

AN - SCOPUS:84994389315

VL - 11

SP - 115

EP - 124

JO - Hepatology International

JF - Hepatology International

SN - 1936-0533

IS - 1

ER -