title: Fas engagement increases expression of interleukin-6 in human glioma cells.
abstract: Although Fas (APO-1/CD95) is expressed ubiquitously and induces cell death, it is also known to mediate other responses such as inflammation and angiogenesis in vivo. Previously, we have reported that Fas ligation induces selective expression of chemokines (IL-8 and MCP-1) in human astroglioma cells in vitro. In this study, we investigated whether Fas ligation can induce expression of other cytokines. Expression of IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, IFN-beta, IFN-gamma, LT-beta, TGF-beta, TNF-a and TNF-beta mRNA levels in CRT-MG human astroglioma cells upon Fas ligation was investigated using RNase protection assay (RPA). We found that IL-6 mRNA is selectively induced upon Fas ligation, and IL-6 mRNA and protein expression was further investigated using single probe RPA and ELISA. To investigate the in vivo expression of IL-6, human brain specimens were homogenized and ELISA was performed for IL-6 expression. Herein, we demonstrate that: (1) Among these cytokines, only IL-6 was induced upon Fas ligation in a dose- and time-dependent manner; (2) A selective p38 MAP kinase inhibitor, SB202190, and a MEK inhibitor, U0126, suppressed induction of IL-6 mRNA and protein expression by Fas ligation; and (3) Glioblastoma multiforme samples (n = 11) contain significantly higher levels of IL-6 compared to those of control brains (n = 5), which correlate with increased levels of Fas. These results suggest that the Fas-FasL system may play a role in the regulation of tumor growth and survival by inducing the pleiotropic cytokine IL-6.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, 35294-0005, USA. cchoi@uab.edu
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Van Wagoner
authors.forename: Etty N
authors.initials: EN
authors.lastname: Benveniste
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019014:fas Receptor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases