title: Tumor Necrosis Factor-alpha- and interleukin-1-induced cellular responses: coupling proteomic and genomic information.
abstract: The pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNFalpha) and Interleukin-1 (IL-1) mediate the innate immune response. Dysregulation of the innate immune response contributes to the pathogenesis of cancer, arthritis, and congestive heart failure. TNFalpha- and IL-1-induced changes in gene expression are mediated by similar transcription factors; however, TNFalpha and IL-1 receptor knock-out mice differ in their sensitivities to a known initiator (lipopolysaccharide, LPS) of the innate immune response. The contrasting responses to LPS indicate that TNFalpha and IL-1 regulate different processes. A large-scale proteomic analysis of TNFalpha- and IL-1-induced responses was undertaken to identify processes uniquely regulated by TNFalpha and IL-1. When combined with genomic studies, our results indicate that TNFalpha, but not IL-1, mediates cell cycle arrest.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, MS 4053, Indianapolis, Indiana 46202, USA.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Ott
authors.forename: Katheryn A
authors.initials: KA
authors.lastname: Resing
authors.forename: Alecia W
authors.initials: AW
authors.lastname: Sizemore
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Heyen
authors.forename: Ross R
authors.initials: RR
authors.lastname: Cocklin
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Pedrick
authors.forename: H Cary
authors.initials: HC
authors.lastname: Woods
authors.forename: Jake Y
authors.initials: JY
authors.lastname: Chen
authors.forename: Mark G
authors.initials: MG
authors.lastname: Goebl
authors.forename: Frank A
authors.initials: FA
authors.lastname: Witzmann
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Harrington
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D023281:Genomics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D051336:Mitochondrial Membranes / Q000187:drug effects; D011506:Proteins / Q000032:analysis / Q000235:genetics; D040901:Proteomics; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007375:Interleukin-1; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha