Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-gamma

Mol Immunol. 1997 Jan;34(1):75-91. doi: 10.1016/s0161-5890(96)00079-x.


IgA is transported into external secretions by the polymeric Ig receptor (pIgR). Interferon-gamma (IFN-gamma), a major regulator of pIgR expression, has been shown to increase pIgR mRNA levels in HT-29 human colon carcinoma cells. To determine the molecular mechanisms of pIgR regulation, genomic DNA containing the 5'-flanking region of the human pIgR gene was isolated and a single start site of transcription in human intestinal epithelial cells was identified. Using chimeric reporter plasmids containing flanking regions of the pIgR gene, a segment of the pIgR promoter which is necessary and sufficient for induction of transcription by IFN-gamma in HT-29 cells was identified. Significantly, the pIgR promoter contains three motifs homologous to the interferon-stimulated response element (ISRE), two in the 5'-flanking region and one in exon 1 of the pIgR gene. The upstream ISREs bind nuclear protein(s) which are constitutively expressed by HT-29 cells, while the exon 1 ISRE binds interferon regulatory factor-1 (IRF-1), following stimulation with IFN-gamma. Furthermore, induction of the IRF-1 promoter by IFN-gamma correlates with induction of the pIgR promoter by IFN-gamma. It has previously been demonstrated that induction of pIgR mRNA by IFN-gamma, requires de novo protein synthesis. It is now shown that IRF-1 is not detected in nuclear extracts from HT-29 cells stimulated with IFN-gamma in the presence of cycloheximide, suggesting that de novo synthesis of IRF-1 is required for induction of pIgR transcription by IFN-gamma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cycloheximide / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Exons / immunology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • HT29 Cells
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon-gamma / pharmacology*
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / immunology
  • Receptors, Polymeric Immunoglobulin / biosynthesis
  • Receptors, Polymeric Immunoglobulin / drug effects
  • Receptors, Polymeric Immunoglobulin / genetics*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / immunology*


  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Nuclear Proteins
  • Phosphoproteins
  • Receptors, Polymeric Immunoglobulin
  • Interferon-gamma
  • Cycloheximide

Associated data

  • GENBANK/Y08254