Induction of ICAM-1 by Armillariella mellea is mediated through generation of reactive oxygen species and JNK activation

• Published in: Journal of ethnopharmacology 2010-03, Vol.128 (1), p.198-205
• Main Authors: Kim, Young Sook, Im, Jintaek, Choi, Jung Nam, Kang, Seok-Seong, Lee, Yeo Jin, Lee, Choong Hwan, Yun, Cheol-Heui, Son, Chang Gue, Han, Seung Hyun
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Agaricales; animal proteins; Armillaria mellea; Armillariella mellea; Base Sequence; biochemical pathways; Biological and medical sciences; Blotting, Western; Cell Line; cell-surface proteins; cellular adhesion molecules; DNA Primers; dosage; dose response; Enzyme Activation; extracts; Flow Cytometry; Gas Chromatography-Mass Spectrometry; General pharmacology; herbal medicines; human cell lines; Humans; immune response; Immuno-regulation; inflammation; Intercellular adhesion molecule-1; Intercellular Adhesion Molecule-1 - biosynthesis; MAP kinase; MAP Kinase Kinase 4 - metabolism; Medical sciences; Medicinal mushroom; medicinal properties; membrane proteins; messenger RNA; monocytes; mushrooms; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; protein synthesis; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; signal transduction; temporal variation; traditional medicine; transcription (genetics); Transcription factors
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.01.011

Armillariella mellea induces the expression of ICAM-1 on monocytes through signaling pathways via reactive oxygen species and JNK. Armillariella mellea is an edible mushroom that has been traditionally used as an alternative medicine in many countries because of its anti-microbial and anti-cancer effects. In this study, we examined the ability of Armillariella mellea to induce the expression of intercellular adhesion molecule (ICAM)-1, an important cellular adhesion molecule for the recruitment of immune cells to regional inflammatory sites. A human monocytic cell line, THP-1 or human peripheral blood mononuclear cells (PBMC) were stimulated with Armillariella mellea extract (AME) and subjected to flow cytometry to examine the expression of ICAM-1 protein on the cell surface. Steady-state mRNA level of ICAM-1 was determined by real-time reverse transcription-polymerase chain reaction. The phosphorylation of JNK protein was examined by Western blot analysis using antibodies specific for non-phosphorylated and phosphorylated forms of JNK. For the analysis of transcription factors regulating ICAM-1 transcription, the nuclear fraction was extracted from AME-treated THP-1 cells and subjected to electrophoretic mobility shift assay. AME induced expression of ICAM-1 and its mRNA in THP-1 cells in dose- and time-dependent manners. AME-induced ICAM-1 expression was also observed on CD14-positive monocytes in human PBMC. Interestingly, AME-induced ICAM-1 production was inhibited by the specific inhibitors of reactive oxygen species (ROS) and JNK, whereas no inhibitory effect was observed when inhibitors of ERK, p38 kinase, phosphatidylinositol 3-kinase, or protein kinase C were used. Concomitantly, AME increased phosphorylation of JNK in a time-dependent fashion. DNA binding activities of NF-κB, AP-1, SP-1, and STAT-1 were increased by AME treatment. These results suggest that AME induces ICAM-1 expression in human monocytic cells through ROS/JNK-dependent signaling pathways leading to the activation of NF-κB, AP-1, SP-1, and STAT-1 transcription factors.