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Inhibitory effect of FSLLRY-NH2 on inflammatory responses induced by hydrogen peroxide in HepG2 cells

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Abstract

Proteinase activated receptor 2 (PAR2), which is localized in the GI tract, the respiratory system, and the kidney tubules is a G protein-coupled receptor associated with inflammation, metabolism, and disease. The aim of this study was to explore the role of PAR2 in hydrogen peroxide (H2O2)-induced HepG2 cells by using FSLLRY-NH2 a PAR2 antagonist. H2O2 treatment resulted in induction of PAR2 in esophageal, gastric, and liver cells, with the most robust response being in HepG2 cells. Furthermore, this effect was dose-dependent in HepG2 cells. Treatment with H2O2 at concentrations above 400 μM for 24 h also reduced HepG2 cell viability. H2O2 treatment increased both the protein and mRNA levels of IL-1β, IL-8, and TNF-α, as well as those of SAPK/JNK. The increased levels of these pro-inflammatory genes and SAPK/JNK induced by H2O2 were attenuated in a dose-dependent manner when cells were co-treated with H2O2 and FSLLRY-NH2. In summary, the PAR2 antagonist peptide, FSLLRY-NH2, reduces the level of the pro-inflammatory genes IL-8, IL-1β, and TNF-α induced by H2O2, through the SAPK/JNK pathways in HepG2 cells. These data suggest that a PAR2 antagonist could be an anti-inflammatory agent in HepG2 cells.

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Acknowledgements

Sung Hee Lee aided in part initial writing of manuscript. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology [Grant 2016R1D1A1A09918019], and by the Chung-Ang University Graduate Research Scholarship in 2016.

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  1. Yeon Joo Lee and Su Jin Kim contributed equally to this study.

Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Republic of Korea

    Yeon Joo Lee, Su Jin Kim, Kyoung Wan Kwon, Won Mo Lee, Wi Joon Im & Uy Dong Sohn

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  1. Yeon Joo Lee
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Correspondence to Uy Dong Sohn.

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Lee, Y.J., Kim, S.J., Kwon, K.W. et al. Inhibitory effect of FSLLRY-NH2 on inflammatory responses induced by hydrogen peroxide in HepG2 cells. Arch. Pharm. Res. 40, 854–863 (2017). https://doi.org/10.1007/s12272-017-0927-9

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