Tumor Necrosis Factor-alpha- and interleukin-1-induced cellular responses: coupling proteomic and genomic information.
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.
Ott
Lee W
LW
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, MS 4053, Indianapolis, Indiana 46202, USA.
Resing
Katheryn A
KA
Sizemore
Alecia W
AW
Heyen
Joshua W
JW
Cocklin
Ross R
RR
Pedrick
Nathan M
NM
Woods
H Cary
HC
Chen
Jake Y
JY
Goebl
Mark G
MG
Witzmann
Frank A
FA
Harrington
Maureen A
MA
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*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007375:Interleukin-1; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha