Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation.
Interferon Regulatory Factor (IRF)-1 is a multifunctional transcription factor, involved in cell growth regulation, pathogen response and immune activation. To identify novel gene targets that may contribute to IRF-1 mediated activities, RNA fingerprinting was performed using NIH3T3 cells that inducibly express a hybrid form of IRF-1 under tetracycline regulated control. Secretory leukocyte protease inhibitor (SLPI) - a regulator of inflammation and an inhibitor of the LPS response - was identified as a gene repressed after doxycycline induced IRF-1 expression. Preliminary analysis of the human SLPI promoter identified an ISRE-like site located within the -221 to -200 region to which IRF-1 binds and a second, putative IRF-1 binding site upstream of the TATA box. Furthermore, co-transfection studies demonstrated that SLPI expression was inhibited by IRF-1 co-expression. The identification of SLPI as a target of IRF-1 regulation reveals a unique involvement of IRF-1 in repression of gene transcription and assigns a novel role for IRF-1 in inflammation.
Nguyen
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Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada.
Teskey
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L
Lin
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Hiscott
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J
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D010750:Phosphoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse; D014157:Transcription Factors