Interleukin‐4 and interferon‐γ synergistically increase secretory component gene expression, but are additive in stimulating secretory immunoglobulin A release by Calu‐3 airway epithelial cells

Loman, Stoffer; Jansen, Henk M.; Out, Theo A.; Lutter, René

doi:10.1046/j.1365-2567.1999.00731.x

Cited by 38 publications

(23 citation statements)

References 41 publications

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“…Synergistically with IFN-c, IL-4 upregulates SC expression on HT-29 colon carcinoma cells [42] and Calu-3 cells [45], while the effects of these cytokines appeared additive on IgA transport. TNF-a and IL-1b also enhance SC expression, but to a lesser extent than IFN-c.…”

Section: Immunoglobulin-a Transportmentioning

confidence: 99%

Lung mucosal immunity: immunoglobulin-A revisited

et al. 2001

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Mucosal defence mechanisms are critical in preventing colonization of the respiratory tract by pathogens and penetration of antigens through the epithelial barrier. Recent research has now illustrated the active contribution of the respiratory epithelium to the exclusion of microbes and particles, but also to the control of the inflammatory and immune responses in the airways and in the alveoli. Epithelial cells also mediate the active transport of polymeric immunoglobulin-A from the lamina propria to the airway lumen through the polymeric immunoglobulin receptor. The role of IgA in the defence of mucosal surfaces has now expanded from a limited role of scavenger of exogenous material to a broader protective function with potential applications in immunotherapy. In addition, the recent identification of receptors for IgA on the surface of blood leukocytes and alveolar macrophages provides an additional mechanism of interaction between the cellular and humoral immune systems at the level of the respiratory tract.

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Section: Immunoglobulin-a Transportmentioning

confidence: 99%

Lung mucosal immunity: immunoglobulin-A revisited

et al. 2001

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“…Such cytokine-mediated up-regulation of pIgR is known to depend on de novo protein synthesis (8 -11), and has recently been shown to take place at the level of transcription in which IL-4 had the greatest effect on the transcription rate of the tested cytokines (10). This effect of IL-4 has been observed both in a human lung carcinoma cell line, Calu-3 (11,12), and in a human colonic carcinoma cell line, HT-29 (13,14). Furthermore, IL-4-mediated up-regulation of pIgR is known to be sensitive to inhibitors of tyrosine phosphorylation, indicating a signaling pathway dependent on protein tyrosine phosphorylation (11,15).…”

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confidence: 99%

Mechanism of IL-4-Mediated Up-Regulation of the Polymeric Ig Receptor: Role of STAT6 in Cell Type-Specific Delayed Transcriptional Response

Schjerven

Brandtzæg

Johansen

2000

The Journal of Immunology

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The polymeric IgR (pIgR) mediates transport of dimeric IgA and pentameric IgM across mucosal epithelia, thereby generating secretory Abs. Its expression is up-regulated at the transcriptional level by IL-4 in HT-29 cells. In this study, we demonstrate that IL-4 mediates up-regulation of human pIgR through a 554-bp IL-4-responsive enhancer in intron 1. Mutation of a binding site for STAT-6 within this region abolished IL-4-induced enhancement, while an adjacent putative C/EBP site was dispensable. IL-4 treatment induced binding of STAT6 to the intronic STAT6 site, but cooperation with nearby upstream and downstream DNA elements was required for IL-4 responsiveness. Furthermore, IL-4-mediated increased transcription of the pIgR-derived enhancer, like the endogenous pIgR gene, required de novo protein synthesis. Interestingly, a conditionally active form of STAT6 sufficed to activate a pIgR-derived enhancer in HT-29 cells, but not in Cos-1 cells, suggesting a requirement for cell type-specific factors. Thus, STAT6 activation mediates a delayed transcriptional enhancement of pIgR by induction of a de novo synthesized protein that cooperates with STAT6 itself bound to its cognate DNA element in intron 1. This mechanism may represent a general strategy for how pleiotropic cytokines elicit cell type-specific transcriptional responses.

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“…dIgA can be found in urine, suggesting that it can reach the urinary space by pIgR-mediated transcytosis (21). pIgR expression has been shown to be regulated by IL-4, TNF-␣, and IFN-␥ in airway, intestinal, and mammary gland epithelial cells (22), and a STAT6 binding domain has been identified in intron 1 of the pIgR gene (23,24). Altogether, these data suggest that the kidney can use the dIgA/pIgR system and that it can be up-regulated to protect the urinary space against pathogens.…”

mentioning

confidence: 99%