Cutting edge: coordinate regulation of IFN regulatory factor-1 and the polymeric Ig receptor by proinflammatory cytokines.
The polymeric IgR (pIgR) mediates transcytosis of IgA across epithelial barriers of mucous membranes and exocrine glands. Synthesis of pIgR is up-regulated by the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-1 in HT-29 human colon carcinoma cells. We previously reported that IFN-gamma and TNF-alpha induce production of the transcription factor IFN regulatory factor-1 (IRF-1) in HT-29 cells and that IRF-1 binds to an element in exon 1 of the PIGR gene. We now report that levels of IRF-1 and pIgR mRNA are coordinately regulated in HT-29 cells by TNF-alpha, IFN-gamma, and IL-1beta. Furthermore, we demonstrate that in vivo expression of pIgR mRNA is greatly depressed in the intestine and liver of IRF-1-deficient mice. Our findings indicate a major role for the IRF-1 transcription factor in regulation of the PIGR gene and suggest a model for regulation of important genes in the mucosal immune system by proinflammatory cytokines.
Blanch
V J
VJ
Department of Microbiology/Immunology, University of Kentucky, Lexington, KY 40536, USA.
Piskurich
J F
JF
Kaetzel
C S
CS
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D018928:Immunity, Mucosal; D018836:Inflammation Mediators / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology