09 August 2018 : Laboratory Research
Inhibition of Epidermal Growth Factor Receptor (EGFR) Reduces Lipopolysaccharide (LPS)-Induced Activation and Inflammatory Cytokines in Hepatic Stellate Cells In Vitro
Yuanyuan Qian1BCD, Jibo Han2AEF, Liqin Zhou1BC, Qi Yu1BD, Jianjiang Xu2DE, Zhigang Jin1DF, Yifeng Yang1AB, Liqin Jiang2DEF*, Dayong Lou1AEFDOI: 10.12659/MSM.909901
Med Sci Monit 2018; 24: LBR5533-5541
Abstract
BACKGROUND: Epidermal growth factor receptor (EGFR) expression is associated with hepatic fibrogenesis. Activated hepatic stellate cells (HSCs) release inflammatory cytokines and extracellular matrix (ECM). The aim of this in vitro study was to investigate HSCs, activated by lipopolysaccharide (LPS), and the role of EGFR using the small molecule EGFR inhibitor, AG1478, and using knockdown of the EGFR gene using small interfering RNA (siRNA) cell transfection.
MATERIAL AND METHODS: HSCs, isolated from male Sprague-Dawley rats, were cultured and treated with and without LPS (100 ng/mL), with and without AG1478 (2.5 μM and 5.0 μM) Cell survival and proliferation were studied using an MTT assay. Western blot was used to measure levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IκBα, cytoplasm and nuclear NFκB and EGFR in the cell lysates before and after small interfering RNA (siRNA) transfection. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of transforming growth factor (TGF)-β, Col-1, and α-smooth muscle actin (SMA). The Toll-like receptor 4 (TLR4) antagonist TAK-242 and the selective c-Src inhibitor, PP2 in LPS induced-EGFR phosphorylation was evaluated using Western blot.
RESULTS: Inhibition of EGFR decreased LPS-induced HSC proliferation and inflammatory cytokines. The TLR4 antagonist TAK-242, and the c-Src inhibitor, PP2 reduced EGFR activation of HSCs, indicating a possible role for the TLR4/c-Src signaling cascade in LPS-induced HSC activation.
CONCLUSIONS: Activation of HSCs by LPS in vitro, including the expression of inflammatory cytokines and mediators of fibrogenesis, were shown to be dependent on the expression of EGFR.
Keywords: Fibrosis, hepatic stellate cells, Receptor, Epidermal Growth Factor
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
11 Mar 2024 : Clinical Research
Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective AdditiveMed Sci Monit In Press; DOI: 10.12659/MSM.942946
12 Mar 2024 : Database Analysis
Risk Factors of Age-Related Macular Degeneration in a Population-Based Study: Results from SHIP-TREND-1 (St...Med Sci Monit In Press; DOI: 10.12659/MSM.943140
12 Mar 2024 : Clinical Research
Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Pa...Med Sci Monit In Press; DOI: 10.12659/MSM.943126
12 Mar 2024 : Clinical Research
Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury Afte...Med Sci Monit In Press; DOI: 10.12659/MSM.943500
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952