Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines

Padberg, Florian; Hering, Henrik; Luch, Andreas; Zellmer, Sebastian

doi:10.1016/j.tiv.2020.104957

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…This highly sensitive model was developed several years ago in which HepG2 and THP-1 cells are co-cultured. In this model, the THP-1 cells act like the liver and the communication between the hepatocytes and the liver is successfully simulated (Granitzny et al 2017 ; Padberg et al 2020 ; Wewering et al 2017 ). Therefore, the HepG2/THP-1 co-culture model is more sensitive than monolayer cell models in detecting immune-mediated liver injury and provides a result closer to the in vivo response.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, the toxic effects of PMMA on the human liver were investigated using the HepG2/THP-1 macrophage co-culture model, which is a sensitive immune-mediated liver injury model. This highly sensitive model was developed a few years ago in which HepG2 and differentiated THP-1 monocytes were co-cultured, where the differentiated THP-1 cells acquire macrophage characteristics and act like the Kuppfer cells, so the communication between the immune system and the liver is successfully simulated (Granitzny et al 2017 ; Padberg et al 2020 ; Wewering et al 2017 ). Therefore, the HepG2/THP-1 co-culture model is more sensitive than monolayer cell models in detecting immune-mediated liver injury and provides a result closer to the in vivo response.…”

Section: Introductionmentioning

confidence: 99%

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An evaluation of a hepatotoxicity risk induced by the microplastic polymethyl methacrylate (PMMA) using HepG2/THP-1 co-culture model

Boran,

Zengin,

Seker

et al. 2024

Environ Sci Pollut Res

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Inappropriate disposal of plastic wastes and their durability in nature cause uncontrolled accumulation of plastic in land/marine ecosystems, also causing destructive effects by bioaccumulating along the food chain. Microplastics may cause chronic inflammation in relation to their permanent structures, especially through oxidative stress and cytotoxic cellular damage, which could increase the risk of cancer development. The accumulation of microplastics in the liver is a major concern, and therefore, the identification of the mechanisms of their hepatotoxic effects is of great importance. Polymethyl methacrylate (PMMA) is a widely used thermoplastic. It has been determined that PMMA disrupts lipid metabolism in the liver in various aquatic organisms and causes reproductive and developmental toxicity. PMMA-induced hepatotoxic effects in humans have not yet been clarified. In our study, the toxic effects of PMMA (in the range of 3–10 μm) on the human liver were investigated using the HepG2/THP-1 macrophage co-culture model, which is a sensitive immune-mediated liver injury model. Cellular uptake of micro-sized PMMA in the cells was done by transmission electron microscopy. Determination of its effects on cell viability and inflammatory response, oxidative stress, along with gene and protein expression levels that play a role in the mechanism pathways underlying the effects were investigated. The results concluded that inflammation, oxidative stress, and disruptions in lipid metabolism should be the focus of attention as important underlying causes of PMMA-induced hepatotoxicity. Our study, which points out the potential adverse effects of microplastics on human health, supports the literature information on the subject.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An evaluation of a hepatotoxicity risk induced by the microplastic polymethyl methacrylate (PMMA) using HepG2/THP-1 co-culture model

Boran,

Zengin,

Seker

et al. 2024

Environ Sci Pollut Res

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“…In this context, the use of THP‐1 cells (a well‐characterized monocytes cell line derived from an acute leukemia patient) was reported. [ 86 ] Alternatively to human cells, murine immune cells can also be exploited to substitute Kupffer cells when modeling the liver. In this sense, both primary mouse peritoneal macrophages, and RAW 264.7 cell line (a monocyte/macrophage‐like line, derived from BALB/c mice cells transformed with Abelson leukemia virus) have been proposed as robust alternatives to human macrophage, due to the similarity of their behavior to one of human cells, as well as to their capability to perform pinocytosis and phagocytosis.…”

Section: Employed Technologies and Methods For The 3d‐bioprinting Of ...mentioning

confidence: 99%

Toward 3D‐Bioprinted Models of the Liver to Boost Drug Development

Guagliano

Volpini

Briatico‐Vangosa

et al. 2022

Macromolecular Bioscience

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The main problems in drug development are connected to enormous costs related to the paltry success rate. The current situation empowered the development of high-throughput and reliable instruments, in addition to the current golden standards, able to predict the failures in the early preclinical phase. Being hepatotoxicity responsible for the failure of 30% of clinical trials, and the 21% of withdrawal of marketed drugs, the development of complex in vitro models (CIVMs) of liver is currently one of the hottest topics in the field. Among the different fabrication techniques, 3D-bioprinting is emerging as a powerful ally for their production, allowing the manufacture of three-dimensional constructs characterized by computer-controlled and customized geometry, and inter-batches reproducibility. Thanks to these, it is possible to rapidly produce tailored cell-laden constructs, to be cultured within static and dynamic systems, thus reaching a further degree of personalization when designing in vitro models. This review highlights and prioritizes the most recent advances related to the development of CIVMs of the hepatic environment to be specifically applied to pharmaceutical research, with a special focus on 3D-bioprinting, since the liver is primarily involved in the metabolism of drugs.

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Response of the Sirtuin/PXR signaling pathway in Mugilogobius chulae exposed to environmentally relevant concentration Paracetamol

Xie

Wang

et al. 2022

Aquatic Toxicology

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Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines

Cited by 6 publications

References 48 publications

An evaluation of a hepatotoxicity risk induced by the microplastic polymethyl methacrylate (PMMA) using HepG2/THP-1 co-culture model

An evaluation of a hepatotoxicity risk induced by the microplastic polymethyl methacrylate (PMMA) using HepG2/THP-1 co-culture model

Toward 3D‐Bioprinted Models of the Liver to Boost Drug Development

Response of the Sirtuin/PXR signaling pathway in Mugilogobius chulae exposed to environmentally relevant concentration Paracetamol

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