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24. In vitro modeling of liver fibrosis with 3D co‐culture system using a novel human hepatic stellate cell line.

Author

Lee, Ho‐Joon, Mun, Seon Ju, Jung, Cho‐Rok, Kang, Hyun‐Mi, Kwon, Jae‐Eun, Ryu, Jae‐Sung, Ahn, Hyo‐Suk, Kwon, Ok‐Seon, Ahn, Jiwon, Moon, Kyung‐Sik, Son, Myung Jin, and Chung, Kyung‐Sook

Abstract

Hepatic stellate cells (HSCs) play an important role in liver fibrosis; however, owing to the heterogeneity and limited supply of primary HSCs, the development of in vitro liver fibrosis models has been impeded. In this study, we established and characterized a novel human HSC line (LSC‐1), and applied it to various types of three‐dimensional (3D) co‐culture systems with differentiated HepaRG cells. Furthermore, we compared LSC‐1 with a commercially available HSC line on conventional monolayer culture. LSC‐1 exhibited an overall upregulation of the expression of fibrogenic genes along with increased levels of matrix and adhesion proteins, suggesting a myofibroblast‐like or transdifferentiated state. However, activated states reverted to a quiescent‐like phenotype when cultured in different 3D culture formats with a relatively soft microenvironment. Additionally, LSC‐1 exerted an overall positive effect on co‐cultured differentiated HepaRG, which significantly increased hepatic functionality upon long‐term cultivation compared with that achieved with other HSC line. In 3D spheroid culture, LSC‐1 exhibited enhanced responsiveness to transforming growth factor beta 1 exposure that is caused by a different matrix‐related protein expression mechanism. Therefore, the LSC‐1 line developed in this study provides a reliable candidate model that can be used to address unmet needs, such as development of antifibrotic therapies. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Methyl P-Coumarate Ameliorates the Inflammatory Response in Activated-Airway Epithelial Cells and Mice with Allergic Asthma.

Author

Park, Ji-Won, Choi, Jinseon, Lee, Juhyun, Park, Jin-Mi, Kim, Seong-Man, Min, Jae-Hong, Seo, Da-Yun, Goo, Soo-Hyeon, Kim, Ju-Hee, Kwon, Ok-Kyoung, Lee, Kihoon, Ahn, Kyung-Seop, Oh, Sei-Ryang, and Lee, Jae-Won

Subjects
EPITHELIAL cells, INFLAMMATION, MICE, ASTHMA, CULTIVARS, MUCUS
Abstract

Methyl p-coumarate (methyl p-hydroxycinnamate) (MH) is a natural compound found in a variety of plants. In the present study, we evaluated the ameliorative effects of MH on airway inflammation in an experimental model of allergic asthma (AA). In this in vitro study, MH was found to exert anti-inflammatory activity on PMA-stimulated A549 airway epithelial cells by suppressing the secretion of IL-6, IL-8, MCP-1, and ICAM-1. In addition, MH exerted an inhibitory effect not only on NF-κB (p-NF-κB and p-IκB) and AP-1 (p-c-Fos and p-c-Jun) activation but also on A549 cell and EOL-1 cell (eosinophil cell lines) adhesion. In LPS-stimulated RAW264.7 macrophages, MH had an inhibitory effect on TNF-α, IL-1β, IL-6, and MCP-1. The results from in vivo study revealed that the increases in eosinophils/Th2 cytokines/MCP-1 in the bronchoalveolar lavage fluid (BALF) and IgE in the serum of OVA-induced mice with AA were effectively inhibited by MH administration. MH also exerted a reductive effect on the immune cell influx, mucus secretion, and iNOS/COX-2 expression in the lungs of mice with AA. The effects of MH were accompanied by the inactivation of NF-κB. Collectively, the findings of the present study indicated that MH attenuates airway inflammation in mice with AA, suggesting its potential as an adjuvant in asthma therapy. [ABSTRACT FROM AUTHOR]

Published
2022
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38. Anti-Inflammatory Activity of Cajanin, an Isoflavonoid Derivative Isolated from Canavalia lineata Pods.

Author

Hong, Su-Jin, Kwon, Ok-Kyoung, Hwang, Daseul, Goo, Su Hyun, Kim, Doo-Young, Kim, Min Ha, Kim, Soo-Young, Jang, Hyun-Jae, and Oh, Sei-Ryang

Subjects
*ANTI-inflammatory agents, *BIOACTIVE compounds, *PHENOLS, *THERAPEUTICS, *CHEMICAL structure, *FLAVONOIDS
Abstract

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1–3, isoflavonoid derivatives 4–11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1–13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Anti-Inflammatory Effects of Lagerstroemia ovalifolia Teijsm. & Binn. in TNFα/IFNγ-Stimulated Keratinocytes.

Author

Lee, Han-Sol, Paik, Jin-Hyub, Kwon, Ok-Kyoung, Paryanto, Imam, Yuniato, Prasetyawan, Ryu, Hyung Won, Choi, Sang-Ho, Oh, Sei-Ryang, Han, Sang-Bae, Park, Ji-Won, and Ahn, Kyung-Seop

Subjects
CYTOKINES, INTERLEUKINS, REVERSE transcriptase polymerase chain reaction, MEDICINAL plants, ANTI-inflammatory agents, WESTERN immunoblotting, JANUS kinases, ATOPIC dermatitis, TUMOR necrosis factors, ENZYME-linked immunosorbent assay, DNA-binding proteins, PLANT extracts, CELL lines, CHEMOKINES, POLYMERASE chain reaction, PHOSPHORYLATION, PHARMACODYNAMICS
Abstract

Ethnopharmacological Relevance. Atopic dermatitis is a chronic inflammatory skin disease. Lagerstroemia ovalifolia Teijsm. & Binn. (LO) has traditionally been used as an herbal medicine for anti-inflammatory diseases. The effect of LO on atopic dermatitis has not been verified scientifically. We investigated the effects of CHCl3 fraction number 5 of LO (LOC) on atopic dermatitis through cell-based experiments. HaCaT cells were treated with tumor necrosis factor-alpha (TNFα)/interferon-gamma (IFNγ) to induce an inflammatory reaction. Proinflammatory cytokines, interleukin- (IL-) 6, IL-8, and IL-1β and chemokines such as thymus and activation-regulated chemokine (TARC/CCL17), monocyte chemoattractant protein 1 (MCP1/CCL2), and macrophage-derived chemokine (MDC/CCL22) were measured by RT-PCR and ELISA. In addition, the degree of phosphorylation and activation of JAK/STAT1, PI3K/AKT, and nuclear factor-kappa B (NF-κB) were measured by western blot and luciferase assays. The production of inflammatory cytokines and chemokines and activation of the JAK/STAT1, PI3K/AKT, and NF-κB pathways were induced by TNFα/IFNγ in HaCaT cells. Under these conditions, LOC treatment inhibited the production of targeted cytokines and chemokines and decreased the phosphorylation and activation of JAK/STAT1, PI3K/AKT, and NF-κB. These results suggest that LOC reduces the production of proinflammatory cytokines and chemokines by suppressing the JAK/STAT1, PI3K/AKT, and NF-κB pathways. Therefore, LOC may have potential as a drug for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Published
2021
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