Adipose tissue derived stromal stem cell therapy in murine <scp>C</scp>on<scp>A</scp>‐derived hepatitis is dependent on myeloid‐lineage and <scp>CD</scp>4<sup>+</sup><scp>T</scp>‐cell suppression

Higashimoto, Mami; Sakai, Yoshio; Takamura, Masayuki; Usui, Soichiro; Nasti, Alessandro; Yoshida, Keiko; Seki, Akihiro; Komura, Takuya; Honda, Masao; Wada, Takashi; Furuichi, Kengo; Ochiya, Takahiro; Kaneko, Shuichi

doi:10.1002/eji.201343531

Cited by 54 publications

(56 citation statements)

References 27 publications

(29 reference statements)

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“…Mounting evidence suggests that CD4 + T cells are the predominant lymphocytes recruited to liver after the intravenous administration of Con A and that these cells play an important role in Con A-induced hepatitis because their depletion prevents liver damage following Con A injection [14]. Macrophages also play an important role in the induction of Con A-induced hepatitis, as confirmed by depletion treatment [42]. Thus, the suppressions of CD4 + T lymphocytes and macrophage infiltration are therapeutic targets for Con A-induced hepatitis.…”

Section: Discussionmentioning

confidence: 93%

Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

Xue

Chen

Wang

et al. 2015

Cell Physiol Biochem

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Background/Aims: To investigate the effects of emodin on concanavalin A (Con A)-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. Methods: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg) to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4 + and F4/80 + cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-κB in mouse livers and RAW264.7 and EL4 cells were measured. Results: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-12, inducible nitric oxide synthase (iNOS), integrin alpha M (ITGAM), chemokine (C-C motif) ligand 2 (CCL2), macrophage inflammatory protein 2 (MIP-2) and chemokine (CXC motif) receptor 2 (CXCR2). Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4 + and F4/80 + cells infiltrating into the liver as well as the activation of p38 MAPK and NF-κB in Con A-treated mouse livers and RAW264.7 and EL4 cells. Conclusion: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4 + and F4/80 + cells and the activation of the p38 MAPK-NF-κB pathway in CD4 + T cells and macrophages.F. Chen contributes to this work equally.

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Section: Discussionmentioning

confidence: 93%

Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

Xue

Chen

Wang

et al. 2015

Cell Physiol Biochem

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“…The pluripotency of ADRCs was examined using a mouse mesenchymal stem cell functional kit (R&D systems, Minneapolis, MN, USA) [11]. Differentiation into adipocytes was detected by oil red O staining after 14 days of incubation in the presence of adipocyte induction factors (hydrocortisone, isobuthlmethylxanthine, and indomethacin).…”

Section: Cell Culture and Multilineage Differentiating Potentialmentioning

confidence: 99%

Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

et al. 2016

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“…Mesenchymal stem cells are pluripotent somatic cells that are abundant in adipose tissue, bone marrow, and umbilical cord. A unique property of these cells is their ability to differentiate into other cells, such as adipocytes, osteocytes, cardiomyocytes, and hepatocytes, as well as their ability to repair injured organs by inhibiting harmful inflammation . Thus, many basic and translational studies of repair/regenerative therapy using mesenchymal stem cells in various impaired organs and diseases have been conducted.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation

Yamato

Sakai

Mochida

et al. 2019

J of Gastro and Hepatol

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Background and Aim The pathological features of non‐alcoholic steatohepatitis (NASH) have not been determined, so fundamental treatment has not been established. Adipose‐tissue‐derived stromal/stem cells (ADSCs) are beneficial for repair/regenerative therapy of impaired organs because of their immuno‐modulatory capability. In this study, we assessed how liver damage progresses during the early development phase of the murine NASH model and investigated whether ADSCs are preventatively efficacious against the fibrosis progression of NASH. Methods C57BL/6J mice were fed with atherogenic high fat or high‐fat diet 60 developing into NASH or simple steatosis. Their hepatic inflammatory cells (HICs) were analyzed by cDNA microarray. NASH mice were treated with ADSCs injected into spleen when hepatic inflammation was initially observed, and liver samples were analyzed. The effect of ADSCs on the mice hepatic stellate cell (HSC) line stimulated by recombinant IL‐17 and HICs from NASH mice was analyzed. Results The gene expression features of HICs implicated as humoral cytokine mediators of lymphoid cells during NASH development, compared with a simple steatosis model. One of the featured cytokines was IL‐17. The development of hepatic fibrosis was alleviated when NASH mice were treated with ADSCs as well as treated with anti‐IL‐17 antibody, and the frequency of IL‐17‐secreting HICs decreased. NASH‐HICs enhanced proliferation of HSCs, in which proliferation was sensitive to IL‐17 stimulation. The stimulatory effect of NASH‐HICs on the activation of HSCs was attenuated by co‐culture with ADSCs. Conclusion ADSCs treatment prevented progression of NASH fibrosis by suppressing IL‐17‐mediated inflammation, which was associated with HSCs activation.

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Adipose tissue derived stromal stem cell therapy in murine ConA‐derived hepatitis is dependent on myeloid‐lineage and CD4⁺T‐cell suppression

Abstract: Additional supporting information may be found in the online version of this article at the publisher's web-site

Cited by 54 publications

References 27 publications

Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation

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Adipose tissue derived stromal stem cell therapy in murine ConA‐derived hepatitis is dependent on myeloid‐lineage and CD4+T‐cell suppression

Abstract: Additional supporting information may be found in the online version of this article at the publisher's web-site

Cited by 54 publications

References 27 publications

Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway

Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation

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Adipose tissue derived stromal stem cell therapy in murine ConA‐derived hepatitis is dependent on myeloid‐lineage and CD4⁺T‐cell suppression