Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma.
Interleukin 12 (IL-12) is a major inducer of interferon gamma (IFN-gamma) and the principal mediator of T helper 1 (Th1) differentiation. To identify IL-12-regulated genes, which might contribute to Th1 differentiation and IFNG regulation, we employed microarray analysis. Surprisingly, a ubiquitously expressed proprotein convertase (PC), furin, was one of the most consistently IL-12-induced genes in T cells, and among PCs was the only one regulated by this cytokine. Furin was preferentially expressed in differentiated Th1 cells in a Stat4-dependent manner. Expression of furin enhanced IFN-gamma secretion, whereas inhibition of furin interfered with IFN-gamma production. Thus, we conclude that IL-12 induction of furin might represent a new aspect of IFN-gamma regulation and control of Th1 differentiation.
Pesu
Marko
M
MIIB-NIAMS-NIH, Bldg 10, Rm 9N262, 10 Center Dr, Bethesda, MD 20892, USA. pesum@mail.nih.gov
Muul
Linda
L
Kanno
Yuka
Y
O'Shea
John J
JJ
D002454:Cell Differentiation / Q000187:drug effects; D045683:Furin / Q000235:genetics* / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D043484:Proprotein Convertases / Q000235:genetics / Q000502:physiology; D050797:STAT4 Transcription Factor / Q000502:physiology; D018417:Th1 Cells / Q000378:metabolism*
D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D018664:Interleukin-12; D007371:Interferon-gamma; D043484:Proprotein Convertases; D045683:Furin