title: Regulation of the polymeric immunoglobulin receptor by the classical and alternative NF-κB pathways in intestinal epithelial cells.
abstract: The polymeric immunoglobulin receptor (pIgR) transports IgA antibodies across intestinal epithelial cells (IECs). Expression of pIgR is upregulated by proinflammatory signaling pathways via activation of nuclear factor-κB (NF-κB). Here, we examined the contributions of the RelA-dependent classical and RelB-dependent alternative pathways of NF-κB to pIgR regulation in the HT-29 human IEC line following stimulation with tumor necrosis factor (TNF), lipopolysaccharide (LPS; Toll-like receptor 4 (TLR4) ligand), and polyinosinic: polycytidylic acid (pIC; TLR3 ligand). Whereas induction of proinflammatory genes such as interleukin-8 (IL-8) required only RelA, pIgR expression was regulated by complex mechanisms that involved both RelA and RelB. Upregulation of pIgR expression by ligation of the lymphotoxin-β receptor suggested a direct role for the alternative NF-κB pathway. Inhibition of mitogen-activated protein kinases reduced the induction of IL-8, but enhanced the induction of pIgR by TNF and TLR signaling. Regulation of pIgR through unique signaling pathways could allow IECs to sustain high levels of IgA transport while limiting the proinflammatory responses.
authors: Department of Microbiology, Immunology & Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA. mebrun2@uky.edu
authors: M E C
authors: ME
authors: Bruno
authors: A L
authors: AL
authors: Frantz
authors: E W
authors: EW
authors: Rogier
authors: F-E
authors: FE
authors: Johansen
authors: C S
authors: CS
authors: Kaetzel
mesh_terms: D004847:Epithelial Cells / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007155:Immunologic Factors; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D048069:Tumor Necrosis Factors; D019950:Mitogen-Activated Protein Kinase 1