Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells.
The MAF (proto-)oncogene family of basic-leucine zipper transcription factors plays crucial roles in the control of mammalian gene expression and development. Here we analyzed the regulation of the human MAFF gene, coding for a small MAF transcription factor, in uterine smooth muscle cells. We found that MAFF transcript levels are induced by proinflammatory cytokines in PHM1-31 myometrial cells. We observed an important induction by interleukin 1 beta (IL1B) and a weaker upregulation by tumor necrosis factor (TNF), whereas interleukin 6 (IL6) treatment had no effect. Time course experiments revealed a rapid induction of MAFF transcripts within 30 min following IL1B treatment. The presence of actinomycin D inhibited the upregulation, suggesting that regulation of MAFF mRNA levels occurs at the transcriptional level. We generated a MAFF-specific antiserum and determined that MAFF protein was also induced by TNF and IL1B in PHM1-31 cells. In contrast, it was particularly interesting that the transcript and protein levels of the highly homologous MAFG and MAFK genes are not modulated by these cytokines. Our results suggest a possible specific role for MAFF in proinflammatory cytokine-mediated control of myometrial gene expression and provide the first link between a small MAF transcription factor and the inflammatory response.
Massrieh
Wael
W
Lady Davis Institute for Medical Research, Department of Medicine, McGill University, Montreal, Quebec, Canada H3T 1E2.
Derjuga
Anna
A
Doualla-Bell
Florence
F
Ku
Chun-Ying
CY
Sanborn
Barbara M
BM
Blank
Volker
V
D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D050978:Maf Transcription Factors, Small / Q000378:metabolism; D051260:MafF Transcription Factor / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D014158:Transcription, Genetic; D048069:Tumor Necrosis Factors / Q000502:physiology; D015854:Up-Regulation
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; C000715470:MAS1 protein, human; D050978:Maf Transcription Factors, Small; D051260:MafF Transcription Factor; D000090063:Proto-Oncogene Mas; D048069:Tumor Necrosis Factors