title: Protective effects of (-)-epigallocatechin-3-gallate against TNF-α-induced lung inflammation via ROS-dependent ICAM-1 inhibition.
abstract: Oxidative stresses are considered to play an important role in the induction of cell adhesion molecules and proinflammatory cytokines implicated in inflammatory processes. Heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS)-3 exert several biological functions, including antiapoptotic and anti-inflammatory effects. Here, we report that HO-1 and SOCS-3 were induced in A549 cells and human pulmonary alveolar epithelial cells (HPAEpiCs) treated with (-)-epigallocatechin-3-gallate (EGCG). EGCG protected against tumor necrosis factor (TNF)-α-mediated lung inflammation by down-regulation of oxidative stress and intercellular adhesion molecule (ICAM)-1 expression in A549 cells or HPAEpiCs and the lungs of mice. EGCG inhibited TNF-α-induced ICAM-1 expression, THP-1 cells adherence, pulmonary hematoma and leukocyte (eosinophils and neutrophils) count in bronchoalveolar lavage fluid in mice. In addition, EGCG also attenuated TNF-α-induced oxidative stress, p47(phox) translocation, MAPKs activation, and STAT-3 and activating transcription factor (ATF)2 phosphorylation. EGCG also reduced the formation of a TNFR1/TRAF2/Rac1/p47(phox) complex. Moreover, in this study, the observed suppression of TNF-α-stimulated ICAM-1 expression and reactive oxygen species (ROS) generation by EGCG was abrogated by transfection with siRNA of SOCS-3 or HO-1. These results suggested that HO-1 or SOCS-3 functions as a suppressor of TNF-α signaling, not only by inhibiting adhesion molecules expression but also by diminishing intracellular ROS production and STAT-3 and ATF2 activation in A549 cells or HPAEpiCs and the lungs of mice.
authors: Department of Physiology and Pharmacology, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors: I-Ta
authors: IT
authors: Lee
authors: Chih-Chung
authors: CC
authors: Lin
authors: Chi-Yin
authors: CY
authors: Lee
authors: Pei-Wen
authors: PW
authors: Hsieh
authors: Chuen-Mao
authors: CM
authors: Yang
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; D047888:Receptors, Tumor Necrosis Factor, Type I; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002392:Catechin; C045651:epigallocatechin gallate; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D048049:Extracellular Signal-Regulated MAP Kinases