Developmental acquisition of T3-sensitive Na-K-ATPase stimulation by rat alveolar epithelial cells

2007 ◽  
Vol 292 (1) ◽  
pp. L6-L14 ◽  
Author(s):  
Jianxun Lei ◽  
Christine H. Wendt ◽  
Daosheng Fan ◽  
Cary N. Mariash ◽  
David H. Ingbar
Keyword(s):  
Atpase Activity ◽  
Cell Line ◽  
Alveolar Epithelial Cell ◽  
Developmental Regulation ◽  
Fluid Secretion ◽  
Surface Expression ◽  
Alveolar Epithelial Cells ◽  
Cell Surface Expression ◽  
Alveolar Epithelial ◽  
Parallel Increase

Late in gestation, the developing air space epithelium switches from chloride and fluid secretion to sodium and fluid absorption. Absorption requires Na-K-ATPase acting in combination with apical sodium entry mechanisms. Hypothyroidism inhibits perinatal fluid resorption, and thyroid hormone [triiodothyronine (T3)] stimulates adult alveolar epithelial cell (AEC) Na-K-ATPase. This study explored the developmental regulation of Na-K-ATPase by T3 in fetal rat distal lung epithelial (FDLE) cells. T3 increased Na-K-ATPase activity in primary FDLE cells from gestational day 19 [both primary FDLE cells at embryonic day 19 (E19) and the cell line FD19 derived from FDLE cells at E19]. However, T3 did not increase the Na-K-ATPase activity in less mature FDLE cells, including primary E17 and E18 FDLE cells and the cell line FD18 (derived from FDLE cells at E18). Subsequent experiments assessed the T3 signal pathway to define whether it was similar in the late FDLE and adult AEC and to determine the site of the switch in responsiveness to T3. As in adult AEC, in the FD19 cell line, the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked the T3-induced increase in Na-K-ATPase activity and plasma membrane quantity. T3 caused a parallel increase in phosphorylation of Akt at Ser473 in FDLE cells from E19, but not from E17 or E18. In the FD18 cell line, transient expression of a constitutively active mutant of the PI3K catalytic p110 subunit significantly augmented the Na-K-ATPase activity and the cell surface expression of Na-K-ATPase α1 protein. In conclusion, FDLE cells from E17 and E18 lacked T3-sensitive Na-K-ATPase activity but acquired this response at E19. The developmental stimulation of Na-K-ATPase by T3 in rat FDLE cells requires activation of PI3K, and the acquisition of T3 responsiveness may be at PI3K or upstream in the signaling pathway.

Thyroid hormone stimulates Na-K-ATPase activity and its plasma membrane insertion in rat alveolar epithelial cells

2003 ◽  
Vol 285 (3) ◽  
pp. L762-L772 ◽  
Author(s):  
Jianxun Lei ◽  
Sogol Nowbar ◽  
Cary N. Mariash ◽  
David H. Ingbar
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Atpase Activity ◽  
Cell Lines ◽  
Surface Expression ◽  
Hydrolytic Activity ◽  
Alveolar Epithelial Cells ◽  
Cell Surface Expression ◽  
Alveolar Epithelial ◽  
Adult Rat

Na-K-ATPase protein is critical for maintaining cellular ion gradients and volume and for transepithelial ion transport in kidney and lung. Thyroid hormone, 3,3′,5-triiodo-l-thyronine (T3), given for 2 days to adult rats, increases alveolar fluid resorption by 65%, but the mechanism is undefined. We tested the hypothesis that T3 stimulates Na-K-ATPase in adult rat alveolar epithelial cells (AEC), including primary rat alveolar type II (ATII) cells, and determined mechanisms of the T3 effect on the Na-KATPase enzyme using two adult rat AEC cell lines (MP48 and RLE-6TN). T3 at 10-8 and 10-5 M increased significantly hydrolytic activity of Na-K-ATPase in primary ATII cells and both AEC cell lines. The increased activity was dose dependent in the cell lines (10-9-10-4 M) and was detected within 30 min and peaked at 6 h. Maximal increases in Na-K-ATPase activity were twofold in MP48 and RLE-6TN cells at pharmacological T3 of 10-5 and 10-4 M, respectively, but increases were statistically significant at physiological T3 as low as 10-9 M. This effect was T3 specific, because reverse T3 (3,3′,5′-triiodo-l-thyronine) at 10-9-10-4 M had no effect. The T3-induced increase in Na-K-ATPase hydrolytic activity was not blocked by actinomycin D. No significant change in mRNA and total cell protein levels of Na-K-ATPase were detected with 10-9-10-5 M T3 at 6 h. However, T3 increased cell surface expression of Na-K-ATPase α1- or β1-subunit proteins by 1.7- and 2-fold, respectively, and increases in Na-K-ATPase activity and cell surface expression were abolished by brefeldin A. These data indicate that T3 specifically stimulates Na-K-ATPase activity in adult rat AEC. The upregulation involves translocation of Na-K-ATPase to plasma membrane, not increased gene transcription. These results suggest a novel nontranscriptional mechanism for regulation of Na-K-ATPase by thyroid hormone.

scholarly journals Pneumocystis carinii Activates the NF-κB Signaling Pathway in Alveolar Epithelial Cells

2005 ◽  
Vol 73 (5) ◽  
pp. 2766-2777 ◽  
Author(s):  
Jing Wang ◽  
Francis Gigliotti ◽  
Sanjay Maggirwar ◽  
Carl Johnston ◽  
Jacob N. Finkelstein ◽  
...  
Keyword(s):  
Cell Line ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Alveolar Epithelial Cell ◽  
Pneumocystis Carinii ◽  
Specific Inhibitor ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

ABSTRACT Pneumocystis carinii pneumonia (PcP) is a clinically important infection of immunocompromised patients. Although the interaction of Pneumocystis with the alveolar epithelium has been well documented, very little information regarding the epithelial response to Pneumocystis is currently available. In order to study Pneumocystis-epithelium interactions, a murine cell line derived specifically from an alveolar epithelial cell (AEC) was utilized. The coculture of murine AECs with mouse Pneumocystis induced a dose- and time-dependent release of the CXC chemokine MIP-2. Importantly, the specific removal of Pneumocystis from the preparation, or the pretreatment of AECs with sulfasalazine, a potent and specific inhibitor of NF-κB, nearly completely abrogated the chemokine response to Pneumocystis. Since the murine MIP-2 promoter contains consensus κB binding sequences, the ability of Pneumocystis to stimulate NF-κB signaling in AECs was examined. Pneumocystis stimulation of an AEC line stably transfected with a κB-dependent reporter construct triggered the NF-κB signaling pathway and reporter production. These data were confirmed in gel shift assays, providing direct evidence that Pneumocystis induced the nuclear translocation of the p50/p65 heterodimeric form of NF-κB. Maximal NF-κB activation was dependent upon direct contact with viable Pneumocystis organisms. These data demonstrate that Pneumocystis activates NF-κB signaling in AECs and establish a reporter cell line for studying NF-κB activation in AECs. Given the global regulatory functions of the NF-κB family, these findings suggest that Pneumocystis directly alters AEC gene expression in a manner that promotes pulmonary immune and inflammatory responses.

scholarly journals Hypoxia and β2-Agonists Regulate Cell Surface Expression of the Epithelial Sodium Channel in Native Alveolar Epithelial Cells

2002 ◽  
Vol 277 (49) ◽  
pp. 47318-47324 ◽  
Author(s):  
Carole Planès ◽  
Marcel Blot-Chabaud ◽  
Michael A. Matthay ◽  
Sylviane Couette ◽  
Tokujiro Uchida ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Sodium Channel ◽  
Epithelial Sodium Channel ◽  
Surface Expression ◽  
Alveolar Epithelial Cells ◽  
Cell Surface Expression ◽  
Alveolar Epithelial ◽  
Β2 Agonists

scholarly journals Chemokine Production by a Human Alveolar Epithelial Cell Line in Response to Mycobacterium tuberculosis

1998 ◽  
Vol 66 (3) ◽  
pp. 1121-1126 ◽  
Author(s):  
Yuanguang Lin ◽  
Ming Zhang ◽  
Peter F. Barnes
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Epithelial Cell ◽  
Cell Line ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Epithelial Cell Line ◽  
Intracellular Growth ◽  
Chemokine Production ◽  
Alveolar Epithelial ◽  
Human Alveolar Epithelial Cell

ABSTRACT To investigate the role of chemokines during the initial local response to Mycobacterium tuberculosis in the human lung, we studied chemokine production by the human alveolar epithelial cell line A549 after infection with M. tuberculosis. M. tuberculosis-infected A549 cells produced mRNAs and protein for monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) but not mRNAs for macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES. Chemokine production in response to M. tuberculosis was not dependent on production of tumor necrosis factor alpha, IL-1β, or IL-6. Two virulent clinical M. tuberculosis isolates, the virulent laboratory strain H37Rv, and the avirulent strain H37Ra elicited production of comparable concentrations of MCP-1 and IL-8, whereas killed M. tuberculosis and three Mycobacterium avium strains did not. The three virulent M. tuberculosis strains grew more rapidly than the avirulent M. tuberculosisstrain in the alveolar epithelial cell line, and the threeM. avium strains did not grow intracellularly. These findings suggest that intracellular growth is necessary for mycobacteria to elicit production of MCP-1 and IL-8 by alveolar epithelial cells but that virulence and the rate of intracellular growth do not correlate with chemokine production. Alveolar epithelial cells may contribute to the local inflammatory response in human tuberculosis by producing chemokines which attract monocytes, lymphocytes, and polymorphonuclear cells.

scholarly journals Characteristics of Passive Solute Transport across Primary Rat Alveolar Epithelial Cell Monolayers

Membranes ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 331
Author(s):  
Yong Ho Kim ◽  
Kwang-Jin Kim ◽  
David Z. D’Argenio ◽  
Edward D. Crandall
Keyword(s):  
Epithelial Cell ◽  
Tight Junctions ◽  
Pore Radius ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Cell Monolayers ◽  
Alveolar Epithelial ◽  
Epithelial Cell Monolayers ◽  
Hydrophilic Solutes

Primary rat alveolar epithelial cell monolayers (RAECM) were grown without (type I cell-like phenotype, RAECM-I) or with (type II cell-like phenotype, RAECM-II) keratinocyte growth factor to assess passive transport of 11 hydrophilic solutes. We estimated apparent permeability (Papp) in the absence/presence of calcium chelator EGTA to determine the effects of perturbing tight junctions on “equivalent” pores. Papp across RAECM-I and -II in the absence of EGTA are similar and decrease as solute size increases. We modeled Papp of the hydrophilic solutes across RAECM-I/-II as taking place via heterogeneous populations of equivalent pores comprised of small (0.41/0.32 nm radius) and large (9.88/11.56 nm radius) pores, respectively. Total equivalent pore area is dominated by small equivalent pores (99.92–99.97%). The number of small and large equivalent pores in RAECM-I was 8.55 and 1.29 times greater, respectively, than those in RAECM-II. With EGTA, the large pore radius in RAECM-I/-II increased by 1.58/4.34 times and the small equivalent pore radius increased by 1.84/1.90 times, respectively. These results indicate that passive diffusion of hydrophilic solutes across an alveolar epithelium occurs via small and large equivalent pores, reflecting interactions of transmembrane proteins expressed in intercellular tight junctions of alveolar epithelial cells.

scholarly journals Senescence associated long non-coding RNA 1 regulates cigarette smoke-induced senescence of type II alveolar epithelial cells through sirtuin-1 signaling

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098604
Author(s):  
Dong Yuan ◽  
Yuanshun Liu ◽  
Mengyu Li ◽  
Hongbin Zhou ◽  
Liming Cao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Sirtuin 1 ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Objective The primary aim of our study was to explore the mechanisms through which long non-coding RNA (lncRNA)-mediated sirtuin-1 (SIRT1) signaling regulates type II alveolar epithelial cell (AECII) senescence induced by a cigarette smoke-media suspension (CSM). Methods Pharmacological SIRT1 activation was induced using SRT2104 and senescence-associated lncRNA 1 (SAL-RNA1) was overexpressed. The expression of SIRT1, FOXO3a, p53, p21, MMP-9, and TIMP-1 in different groups was detected by qRT-PCR and Western blotting; the activity of SA-β gal was detected by staining; the binding of SIRT1 to FOXO3a and p53 gene transcription promoters was detected by Chip. Results We found that CSM increased AECII senescence, while SAL-RNA1 overexpression and SIRT1 activation significantly decreased levels of AECII senescence induced by CSM. Using chromatin immunoprecipitation, we found that SIRT1 bound differentially to transcriptional complexes on the FOXO3a and p53 promoters. Conclusion Our results suggested that lncRNA-SAL1-mediated SIRT1 signaling reduces senescence of AECIIs induced by CSM. These findings suggest a new therapeutic target to limit the irreversible apoptosis of lung epithelial cells in COPD patients.

scholarly journals TRIM72 is required for effective repair of alveolar epithelial cell wounding

2014 ◽  
Vol 307 (6) ◽  
pp. L449-L459 ◽  
Author(s):  
Seong Chul Kim ◽  
Thomas Kellett ◽  
Shaohua Wang ◽  
Miyuki Nishi ◽  
Nagaraja Nagre ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Striated Muscle ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Cells ◽  
Alveolar Epithelial ◽  
High Tidal Volume Ventilation

The molecular mechanisms for lung cell repair are largely unknown. Previous studies identified tripartite motif protein 72 (TRIM72) from striated muscle and linked its function to tissue repair. In this study, we characterized TRIM72 expression in lung tissues and investigated the role of TRIM72 in repair of alveolar epithelial cells. In vivo injury of lung cells was introduced by high tidal volume ventilation, and repair-defective cells were labeled with postinjury administration of propidium iodide. Primary alveolar epithelial cells were isolated and membrane wounding and repair were labeled separately. Our results show that absence of TRIM72 increases susceptibility to deformation-induced lung injury whereas TRIM72 overexpression is protective. In vitro cell wounding assay revealed that TRIM72 protects alveolar epithelial cells through promoting repair rather than increasing resistance to injury. The repair function of TRIM72 in lung cells is further linked to caveolin 1. These data suggest an essential role for TRIM72 in repair of alveolar epithelial cells under plasma membrane stress failure.

Effect of Steroids on the Synthesis of Complement C3 in a Human Alveolar Epithelial Cell Line

1993 ◽  
Vol 19 (5) ◽  
pp. 603-616 ◽  
Author(s):  
Terence L. Zach ◽  
Vicki A. Herrman ◽  
Laura D. Hill ◽  
M. Patricia Leuschen
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Alveolar Epithelial Cell ◽  
Complement C3 ◽  
Epithelial Cell Line ◽  
Alveolar Epithelial ◽  
Human Alveolar Epithelial Cell
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