Forced IFIT-2 expression represses LPS induced TNF-alpha expression at posttranscriptional levels.
BACKGROUND
Interferon induced tetratricopeptide repeat protein 2 (IFIT-2, P54) belongs to the type I interferon response genes and is highly induced after stimulation with LPS. The biological function of this protein is so far unclear. Previous studies indicated that IFIT-2 binds to the initiation factor subunit eIF-3c, affects translation initiation and inhibits protein synthesis. The aim of the study was to further characterize the function of IFIT-2.


RESULTS
Stimulation of RAW264.7 macrophages with LPS or IFN-gamma leads to the expression of IFIT-2 in a type I interferon dependent manner. By using stably transfected RAW264.7 macrophages overexpressing IFIT-2 we found that IFIT-2 inhibits selectively LPS induced expression of TNF-alpha, IL-6, and MIP-2 but not of IFIT-1 or EGR-1. In IFIT-2 overexpressing cells TNF-alpha mRNA expression was lower after LPS stimulation due to reduced mRNA stability. Further experiments suggest that characteristics of the 3'UTR of transcripts discriminate whether IFIT-2 has a strong impact on protein expression or not.


CONCLUSIONS
Our data suggest that IFIT-2 may affect selectively LPS induced protein expression probably by regulation at different posttranscriptional levels.
Berchtold
Susanne
S
Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany. susanne.berchtold@med.uni-tuebingen.de
Manncke
Birgit
B
Klenk
Juliane
J
Geisel
Julia
J
Autenrieth
Ingo B
IB
Bohn
Erwin
E
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D016899:Interferon-beta / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D017384:Sequence Deletion; D015533:Transcriptional Activation / Q000276:immunology*; D014162:Transfection; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C092573:Ifit1 protein, mouse; C092572:Ifit2 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta