Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice

Virginia Maina, Salvatore Sutti, Irene Locatelli, Matteo Vidali, Cristina Mombello, Cristina Bozzola, Emanuele Albano

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In humans, there is large inter-individual variability in the evolution of NAFLD (non-alcoholic fatty liver disease) to NASH (non-alcoholic steatohepatitis). To investigate this issue, NASH was induced with an MCD (methionine-choline-deficient) diet in C57BL/6 and Balb/c mice that are characterized by different biases in Th1/Th2 and macrophage (M1/M2) responses. Following 4 weeks on the MCD diet, steatosis and lobular inflammation were prevalent in C57BL/6 (Th1, M1 oriented) than in Balb/c (Th2, M2 oriented) mice. Consistently, hepatic TNFα (tumour necrosis factor α) mRNA expression and circulating TNFα levels were higher in MCD-fed C57BL/6 than in MCD-fed Balb/c mice. The Th1/Th2 bias did not account for the increased NASH severity, as in both strains MCD feeding did not significantly modify the liver mRNA expression of the Th1 markers IFNγ (interferon γ) and T-bet or that of the Th2 markers IL-4 (interleukin 4) and GATA-3. Conversely, MCD-fed C57BL/6 mice displayed higher liver mRNAs for the macrophage M1 activation markers iNOS (inducible NO synthase), IL-12p40 and CXCL10 (CXC chemokine ligand 10) than similarly treated Balb/c mice, without effects on the M2 polarization markers IL-10 and MGL-1 (macrophage galactose-type C-type lectin-1). Circulating IL-12 was also higher in MCD-fed C57BL/6 than in MCD-fed Balb/c mice. The analysis of macrophages isolated from the livers of MCD-fed animals confirmed an enhanced expression of M1 markers in C57BL/6 mice. Among all of the MCD-treated mice, liver iNOS, IL-12p40 and CXCL10 mRNA levels positively correlated with the frequency of hepatic necro-inflammatory foci. We concluded that the macrophage M1 bias in C57BL/6 mice may account for the increased severity of NASH in this strain, suggesting macrophage responses as important contributors to NAFLD progression.

Original languageEnglish
Pages (from-to)545-553
Number of pages9
JournalClinical Science
Volume122
Issue number11
DOIs
Publication statusPublished - Jun 2012

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Macrophage Activation
Fatty Liver
Choline
Methionine
Macrophages
Liver
Inbred C57BL Mouse
Interleukin-12 Subunit p40
CXC Chemokines
Messenger RNA
Nitric Oxide Synthase
Tumor Necrosis Factor-alpha
Diet
Ligands
C-Type Lectins
Interleukin-12
Galactose
Interleukin-4
Interleukin-10
Interferons

Keywords

  • Cytokine
  • Kuppfer cell
  • Liver inflammation
  • Liver injury
  • Non-alcoholic fatty liver disease
  • Strain difference

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Maina, V., Sutti, S., Locatelli, I., Vidali, M., Mombello, C., Bozzola, C., & Albano, E. (2012). Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice. Clinical Science, 122(11), 545-553. https://doi.org/10.1042/CS20110366

Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice. / Maina, Virginia; Sutti, Salvatore; Locatelli, Irene; Vidali, Matteo; Mombello, Cristina; Bozzola, Cristina; Albano, Emanuele.

In: Clinical Science, Vol. 122, No. 11, 06.2012, p. 545-553.

Research output: Contribution to journalArticle

Maina, V, Sutti, S, Locatelli, I, Vidali, M, Mombello, C, Bozzola, C & Albano, E 2012, 'Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice', Clinical Science, vol. 122, no. 11, pp. 545-553. https://doi.org/10.1042/CS20110366
Maina V, Sutti S, Locatelli I, Vidali M, Mombello C, Bozzola C et al. Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice. Clinical Science. 2012 Jun;122(11):545-553. https://doi.org/10.1042/CS20110366
Maina, Virginia ; Sutti, Salvatore ; Locatelli, Irene ; Vidali, Matteo ; Mombello, Cristina ; Bozzola, Cristina ; Albano, Emanuele. / Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice. In: Clinical Science. 2012 ; Vol. 122, No. 11. pp. 545-553.
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