title: Requirement of caspases and p38 MAPK for TRAIL-mediated ICAM-1 expression by human astroglial cells.
abstract: Among tumor necrosis factor (TNF) superfamily, TNF-related apoptosis inducing ligand (TRAIL) along with TNF-alpha and FasL is known as death ligand due to its selective cytotoxicity against transformed tumor cells. TRAIL can also induce alternative angiogenic and/or proinflammatory signals other than apoptosis, however, the molecular mechanisms responsible for the alternative signals have not been detailed yet. Intercellular adhesion molecule-1 (ICAM-1) is thought to be involved in the processes of metastasis and angiogenesis in various tumors. We investigated the molecular mechanisms responsible for ICAM-1 expression by death ligands in human astroglial cells to delineate the alternative signals of these ligands. Here, we demonstrate that (1) death ligands induced expression of ICAM-1 at the mRNA and protein levels in human astroglial cells; (2) pre-treatment of z-VAD-fmk and/or SB202190 suppressed death ligand-induced ICAM-1 expression and subsequent adhesion of activated monocytic cells; and (3) inhibition of caspase suppressed death ligand-induced phosphorylation of p38 MAPK and IKK. These findings suggest biological function of death receptors other than apoptosis in human astroglial cells, and the involvement of caspase and/or p38 MAPK in alternative signaling through death receptors.
authors.affiliation: Laboratory of Computational Cell Biology, Department of Bio and Brain Engineering, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Kyungsun
authors.initials: K
authors.lastname: Choi
authors.forename: Seungjeong
authors.initials: S
authors.lastname: Song
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001253:Astrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole