IFN-gamma-dependent IL-7 gene regulation in keratinocytes.
IL-7 plays a central role in regulating the growth and differentiation of T cells. We have reported previously that epidermal keratinocytes produce biologically relevant amounts of IL-7, thereby supporting the growth of epidermal gamma delta T cells. In this report, we report that IL-7 gene expression is regulated in keratinocytes by IFN-gamma. Treatment of Pam 212 keratinocytes with IFN-gamma induced a preferential expression of 2.6- and 1.5-kb IL-7 mRNAs, in addition to the 2.9- and 1.7-kb mRNAs that are expressed constitutively. The 2.6- and 1.5-kb mRNAs are produced through the use of alternative transcription initiation sites; these mRNAs are transcribed within 250 bp from the coding sequence, whereas 2.9- and 1.7-kb mRNAs contain > 400 bases in the 5'-untranslated region. IFN-gamma appears to promote this conversion through the IFN-stimulated response element (ISRE), which is located 270 bp upstream from the coding sequence. ISRE is followed by the initiator, a non-TATA-type transcription control element. Functional relevance of the ISRE/initiator complex was suggested by the observations that IFN-gamma-dependent transcription was initiated from immediately downstream of this complex, and that its deletion resulted in an abrogated IFN-gamma responsiveness in transcriptional regulation. These results document a novel mechanism by which IL-7 gene expression is regulated in keratinocytes by a cytokine produced by T cells (IFN-gamma).
Ariizumi
K
K
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Meng
Y
Y
Bergstresser
P R
PR
Takashima
A
A
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D004261:DNA Replication; D018076:DNA, Complementary / Q000032:analysis; D005786:Gene Expression Regulation / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology*; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics*; D015603:Keratinocytes / Q000276:immunology*; D008156:Luciferases / Q000032:analysis; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis
D018076:DNA, Complementary; D015851:Interleukin-7; D012333:RNA, Messenger; D007371:Interferon-gamma; D008156:Luciferases