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Nuclear factor‐κB contributes to interleukin‐4‐ and interferon‐dependent polymeric immunoglobulin receptor expression in human intestinal epithelial cells
Author(s) -
Ackermann Laynez W.,
Denning Gerene M.
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01773.x
Subject(s) - polymeric immunoglobulin receptor , transcytosis , biology , transcription factor , reporter gene , cytokine , immune system , receptor , interferon , microbiology and biotechnology , nf κb , signal transduction , immunology , gene expression , gene , biochemistry , endocytosis
Summary 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‐γ (IFN‐γ). In studies using human intestinal epithelial cells (HT29), multiple inhibitors of the transcription factor nuclear factor‐κB (NF‐κB), including a dominant negative IκBα‐serine mutant, inhibited both IL‐4‐ and IFN‐dependent increases in pIgR expression. Under identical conditions, NF‐κB inhibitors had no effect on cytokine‐dependent increases in expression of the transcription factor interferon regulatory factor‐1. Over‐expression of the IκBα‐serine mutant also inhibited reporter gene expression in response to IL‐4, TNF‐α, IL‐1β, and in some cases IFN‐γ 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‐κB is required. Finally, reporter gene studies with NF‐κB enhancer elements indicated that IFN‐γ alone and IL‐4 in combination with other cytokines activated NF‐κB 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.