Abstract
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.
MeSH Terms
Cell Differentiation/drug effects
Furin/genetics,physiology
Gene Expression Profiling
Gene Expression Regulation/drug effects,immunology
Humans
Interferon-gamma/biosynthesis,metabolism
Interleukin-12/pharmacology
Oligonucleotide Array Sequence Analysis
Proprotein Convertases/genetics,physiology
STAT4 Transcription Factor/physiology
Th1 Cells/metabolism
Chemicals
STAT4 Transcription Factor
STAT4 protein, human
Interleukin-12
Interferon-gamma
Proprotein Convertases
Furin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pesu Marko
MIIB-NIAMS-NIH, Bldg 10, Rm 9N262, 10 Center Dr, Bethesda, MD 20892, USA. pesum@mail.nih.gov
Muul Linda
Kanno Yuka
O'Shea John J
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