Volume Regulation and 'Cross-Talk� in Sodium-Absorbing Epithelial Cells

Author(s):  
St.G. Schultz ◽  
W.P. Dubinsky ◽  
J.-Y. Lapointe
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kristina Andelid ◽  
Karolina Öst ◽  
Anders Andersson ◽  
Esha Mohamed ◽  
Zala Jevnikar ◽  
...  

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air–liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNFα in this cross-talk. Conclusions For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNFα-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.


2016 ◽  
Vol 310 (7) ◽  
pp. C542-C557 ◽  
Author(s):  
Jia Wang ◽  
Liang Han ◽  
James Sinnett-Smith ◽  
Li-Li Han ◽  
Jan V. Stevens ◽  
...  

Given the fundamental role of β-catenin signaling in intestinal epithelial cell proliferation and the growth-promoting function of protein kinase D1 (PKD1) in these cells, we hypothesized that PKDs mediate cross talk with β-catenin signaling. The results presented here provide several lines of evidence supporting this hypothesis. We found that stimulation of intestinal epithelial IEC-18 cells with the G protein-coupled receptor (GPCR) agonist angiotensin II (ANG II), a potent inducer of PKD activation, promoted endogenous β-catenin nuclear localization in a time-dependent manner. A significant increase was evident within 1 h of ANG II stimulation ( P < 0.01), peaked at 4 h ( P < 0.001), and declined afterwards. GPCR stimulation also induced a marked increase in β-catenin-regulated genes and phosphorylation at Ser552 in intestinal epithelial cells. Exposure to preferential inhibitors of the PKD family (CRT006610 or kb NB 142-70) or knockdown of the isoforms of the PKD family prevented the increase in β-catenin nuclear localization and phosphorylation at Ser552 in response to ANG II. GPCR stimulation also induced the formation of a complex between PKD1 and β-catenin, as shown by coimmunoprecipitation that depended on PKD1 catalytic activation, as it was abrogated by cell treatment with PKD family inhibitors. Using transgenic mice that express elevated PKD1 protein in the intestinal epithelium, we detected a marked increase in the localization of β-catenin in the nucleus of crypt epithelial cells in the ileum of PKD1 transgenic mice, compared with nontransgenic littermates. Collectively, our results identify a novel cross talk between PKD and β-catenin in intestinal epithelial cells, both in vitro and in vivo.


2019 ◽  
Vol 18 (5) ◽  
pp. 892-908 ◽  
Author(s):  
Laura M. Palma Medina ◽  
Ann-Kristin Becker ◽  
Stephan Michalik ◽  
Harita Yedavally ◽  
Elisa J.M. Raineri ◽  
...  

2000 ◽  
Vol 10 (5-6) ◽  
pp. 289-296 ◽  
Author(s):  
Thea van der Wijk ◽  
Sebastian F.B. Tomassen ◽  
Hugo R. de Jonge ◽  
Ben C. Tilly

2000 ◽  
Vol 118 (4) ◽  
pp. A239
Author(s):  
Outi Nylander-Koski ◽  
Harri Mustonen ◽  
Tuula Kiviluoto ◽  
Eero Kivilaakso

2012 ◽  
Vol 302 (8) ◽  
pp. F1055-F1062 ◽  
Author(s):  
Farah Tasnim ◽  
Daniele Zink

Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.


2009 ◽  
Vol 21 (9) ◽  
pp. 124
Author(s):  
P. Paiva ◽  
K. Meehan ◽  
L. A. Salamonsen ◽  
E. Dimitriadis

Emerging evidence suggests an important role for the early embryo product human chorionic gonadotrophin (hCG) in embryo-endometrial interactions critical for successful embryo implantation1. The human endometrium is also a source of hCG, with maximal expression of hCG and its receptor, hCG/LHR, in endometrial epithelial cells during the window of implantation in vivo2,3, and in primary endometrial epithelial cells (EECs)3. Implantation is tightly regulated by growth and regulatory factors produced within the embryo-endometrial microenvironment. We hypothesise that embryo/endometrial-derived hCG mediates the molecular cross talk vital for successful implantation. The main objective of this study was to investigate the effect of hCG on the production of a selected cohort of 42 cytokines and growth factors by EECs. These included those with both known and previously unidentified roles during implantation. The secretory profile of cytokines/growth factors produced by EECs was also analysed. EECs (n=8 cultures) were isolated from biopsies collected from fertile cycling women. Cells were treated without or with recombinant hCG for 48 hr and conditioned media collected for quantitative analysis using LuminexTM multiplex technology. For the first time, a secretory profile of 42 cytokines and growth factors produced by EECs was established, as was the identification of fibroblast growth factor-2 (FGF-2) secretion by human endometrial epithelium. hCG (2 IU/ml) significantly increased the production of a number factors including those with known roles during trophoblast migration and adhesion (CX3CL1; 71±31%, CXCL10; 67±24%, CCL4; 87±12%), in trophoblast differentiation (IL-1α ; 68±31%) and with unidentified roles during implantation (CCL22; 78±40%, GM-CSF; 45±16%, FGF-2; 50±25%; all p<0.05). Upregulation of the known hCG regulated proteins, VEGF and LIF, validated this study. These findings clearly support roles for the embryo/endometrium via hCG in actively contributing to the molecular cross-talk during the early stages of implantation.


2019 ◽  
Vol 12 (2) ◽  
pp. 425-433 ◽  
Author(s):  
K. Golebski ◽  
W. Hoepel ◽  
D. van Egmond ◽  
E. J. de Groot ◽  
G. D. Amatngalim ◽  
...  

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