Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation

Kazuhiro Atsukawa, Hidetsugu Saito, Nobuhiro Tsukada, Yasutada Akiba, Kyoko Toda, Naoki Kumagai, Tazuko Ohishi, Yoshitaka Kamegaya, Hiromasa Ishii

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-γ (IFN-γ; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-γ. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-γ treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-γ or IL-4 further enhanced the growth stimulation. These results suggest that IFN-γ and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.

Original languageEnglish
Pages (from-to)193-206
Number of pages14
JournalHepatology Research
Volume22
Issue number2
Publication statusPublished - 2001

Fingerprint

Hepatic Stellate Cells
Kupffer Cells
Giant Cells
Interleukin-4
Cell Proliferation
Cytokines
Liver
Growth
Inbred C57BL Mouse
Lipopolysaccharides
Intercellular Adhesion Molecule-1
Intraperitoneal Injections
Interferons
Fluorescence
Monoclonal Antibodies
Electrons

Keywords

  • Interferon-γ
  • Interleukin-4
  • Kupffer cell
  • Multinucleated giant cell

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation. / Atsukawa, Kazuhiro; Saito, Hidetsugu; Tsukada, Nobuhiro; Akiba, Yasutada; Toda, Kyoko; Kumagai, Naoki; Ohishi, Tazuko; Kamegaya, Yoshitaka; Ishii, Hiromasa.

In: Hepatology Research, Vol. 22, No. 2, 2001, p. 193-206.

Research output: Contribution to journalArticle

Atsukawa, Kazuhiro ; Saito, Hidetsugu ; Tsukada, Nobuhiro ; Akiba, Yasutada ; Toda, Kyoko ; Kumagai, Naoki ; Ohishi, Tazuko ; Kamegaya, Yoshitaka ; Ishii, Hiromasa. / Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation. In: Hepatology Research. 2001 ; Vol. 22, No. 2. pp. 193-206.
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abstract = "To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-γ (IFN-γ; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-γ. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-γ treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-γ or IL-4 further enhanced the growth stimulation. These results suggest that IFN-γ and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.",
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T1 - Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation

AU - Atsukawa, Kazuhiro

AU - Saito, Hidetsugu

AU - Tsukada, Nobuhiro

AU - Akiba, Yasutada

AU - Toda, Kyoko

AU - Kumagai, Naoki

AU - Ohishi, Tazuko

AU - Kamegaya, Yoshitaka

AU - Ishii, Hiromasa

PY - 2001

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AB - To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-γ (IFN-γ; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-γ. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-γ treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-γ or IL-4 further enhanced the growth stimulation. These results suggest that IFN-γ and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.

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KW - Interleukin-4

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