Fig. 4.

Regulation of PIGR gene transcription by cytokines and microbial factors. A mucosal epithelial cell expressing cytokine receptors and Toll-like receptors (TLRs) is shown. These receptors are depicted on one surface of the cell for purposes of illustration; however, it should not be implied that these receptors are localized preferentially to the apical and/or basolateral surface of a polarized epithelial cell. It should further be noted that epithelial cells express a wide range of cytokine and pattern recognition receptors in addition to those illustrated here.Ligation of cytokine receptors and TLRs results in translocation of activated transcription factors to the nucleus and de novo synthesis of additional transcription factors. The cytoplasmic adapter protein MyD88 transduces signals from cytokine receptors in the IL1R superfamily as well as many TLRs. The PIGR gene contains binding sites for members of the Interferon Regulatory Factor (IRF), Signal Transducer and Activator of Transcription (STAT) and Nuclear Factor-κB (NF-κB) families of transcription factors. The signaling pathways that regulate PIGR gene transcription are described in the text.