title: EGCG attenuates pro-inflammatory cytokines and chemokines production in LPS-stimulated L02 hepatocyte.
abstract: Endotoxin lipopolysaccharide (LPS) plays an important role in the acceleration of inflammatory reaction of hepatitis as the second attack. Compounds that can prevent inflammation by targeting LPS have potential therapeutic clinical application. Epigallocatechin-3-gallate (EGCG) has potent hepatocyte-protective effect and mild anti-hepatitis virus function. Here, we investigated whether EGCG attenuated the severity of inflammatory response in LPS-stimulated L02 hepatocytes. L02 hepatocytes were pretreated with EGCG for 2 h, then stimulated by LPS at 250 ng/ml. The expression levels of chemokine regulated upon activation normal T-cell expressed and secreted (Rantes) and monocyte chemotactic protein-1 (MCP-1), pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ, adhesion molecule intercellular adhesion molecule-1 (ICAM-1), oxidant stress molecules nitric oxide (NO), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) were tested by enzyme-linked immunosorbent assay. The expression of total extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-ERK1/2 (p-ERK1/2), p-AKT, total p38, phospho-p38 (p-p38), total p65 and phospho-p65 (p-p65), IκBα, phospho-IκBα (p-IκBα) and TNF receptor associated factor 2 were tested by western blot analysis. Our results showed that pre-treatment with EGCG could significantly reduce the production of TNF-α, Rantes, MCP-1, ICAM-1, NO, VEGF, and MMP-2 in LPS-stimulated L02 hepatocytes in a dose-dependent manner. The effect of EGCG may be related to the inhibition of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by down-regulation of p-IκBα, p65, p-p65, p-p38, p-ERK1/2, and p-AKT. These results indicate that EGCG suppresses LPS-induced inflammatory response and oxidant stress and exerts its hepatocyte-protective activity partially by inhibiting NF-κB and MAPK pathways.
authors.affiliation: State Key Laboratory for Diagnostic and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Qian
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002392:Catechin; C045651:epigallocatechin gallate; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2
keywords: EGCG; L02 hepatocytes; LPS; MAPK pathway; NF-κB pathway