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  • Title: Nuclear factor-kappaB contributes to interleukin-4- and interferon-dependent polymeric immunoglobulin receptor expression in human intestinal epithelial cells.
    Author: Ackermann LW, Denning GM.
    Journal: Immunology; 2004 Jan; 111(1):75-85. PubMed ID: 14678201.
    Abstract:
    Polymeric immunoglobulins (pIgs) that are present at mucosal surfaces play key roles in both the innate and adaptive immune responses. These pIgs are delivered to the mucosal surface via transcytosis across the epithelium, a process mediated by the polymeric immunoglobulin receptor (pIgR). Previous studies demonstrate that expression of the pIgR is regulated by multiple immunomodulatory factors including interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). In studies using human intestinal epithelial cells (HT29), multiple inhibitors of the transcription factor nuclear factor-kappaB (NF-kappaB), including a dominant negative IkappaBalpha-serine mutant, inhibited both IL-4- and IFN-dependent increases in pIgR expression. Under identical conditions, NF-kappaB inhibitors had no effect on cytokine-dependent increases in expression of the transcription factor interferon regulatory factor-1. Over-expression of the IkappaBalpha-serine mutant also inhibited reporter gene expression in response to IL-4, TNF-alpha, IL-1beta, and in some cases IFN-gamma using constructs with sequences from the pIgR promoter. Reduced levels of pIgR were observed even when inhibitors were added >/=24 hr after cytokines suggesting that prolonged activation of NF-kappaB is required. Finally, reporter gene studies with NF-kappaB enhancer elements indicated that IFN-gamma alone and IL-4 in combination with other cytokines activated NF-kappaB in HT29 cells. Together, these studies provide additional insight into the signalling pathways that contribute to expression of the pIgR, a critical player in mucosal immunity.
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