Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-γ

2001 ◽  
Vol 281 (6) ◽  
pp. C2029-C2038 ◽  
Author(s):  
Minoo Ahdieh ◽  
Tim Vandenbos ◽  
Adel Youakim
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Leading Edge ◽  
Lung Epithelial Cells ◽  
Collagen I ◽  
Epithelial Barrier Function ◽  
Lung Epithelial ◽  
Associated Proteins ◽  
Ifn Γ

To understand the effects of cytokines on epithelial cells in asthma, we have investigated the effects of interleukin (IL)-4, IL-13, and interferon (IFN)-γ on barrier function and wound healing in Calu-3 human lung epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on Transwell filters resulted in a 70–75% decrease in barrier function as assessed by electrophysiological and [14C]mannitol flux measurements. In contrast, IFN-γ enhanced barrier function threefold using these same parameters. Cells treated concurrently with IFN-γ and IL-4 or IL-13 showed an initial decline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tight junction-associated proteins ZO-1 and occludin showed that IL-4 and IL-13 significantly reduced ZO-1 expression and modestly decreased occludin expression compared with controls. IFN-γ, quite unexpectedly given its enhancing effect on barrier function, reduced expression of ZO-1 and occludin to almost undetectable levels compared with controls. In wound-healing assays of cells grown on collagen I, IL-4 and IL-13 decreased migration, whereas IFN-γ treatment enhanced migration, compared with control cells. Addition of IFN-γ, in combination with IL-4 or IL-13, restored migration of cells to control levels. Migration differences observed between the various cytokine treatments was correlated with expression of the collagen I-binding α2β1-integrin at the leading edge of cells at the wound front; α2β1-integrin expression was decreased in IFN-γ-treated cells compared with controls, whereas it was highest in IL-4- and IL-13-treated cells. These results demonstrate that IL-4 and IL-13 diminish the capacity of Calu-3 cells to maintain barrier function and repair wounds, whereas IFN-γ promotes epithelial restitution by enhancing barrier function and wound healing.

Microtubule dynamics and Rac-1 signaling independently regulate barrier function in lung epithelial cells

2007 ◽  
Vol 293 (5) ◽  
pp. L1321-L1331 ◽  
Author(s):  
Magdalena J. Lorenowicz ◽  
Mar Fernandez-Borja ◽  
Anne-Marieke D. van Stalborch ◽  
Marian A. J. A. van Sterkenburg ◽  
Pieter S. Hiemstra ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Lung Epithelial Cells ◽  
Cell Junctions ◽  
Epithelial Barrier ◽  
Cell Contact ◽  
Epithelial Barrier Function ◽  
Lung Epithelial ◽  
Cell Cell

Cadherin-mediated cell-cell adhesion controls the morphology and function of epithelial cells and is a critical component of the pathology of chronic inflammatory disorders. Dynamic interactions between cadherins and the actin cytoskeleton are required for stable cell-cell contact. Besides actin, microtubules also target intercellular, cadherin-based junctions and contribute to their formation and stability. Here, we studied the role of microtubules in conjunction with Rho-like GTPases in the regulation of lung epithelial barrier function using real-time monitoring of transepithelial electrical resistance. Unexpectedly, we found that disruption of microtubules promotes epithelial cell-cell adhesion. This increase in epithelial barrier function is accompanied by the accumulation of β-catenin at cell-cell junctions, as detected by immunofluorescence. Moreover, we found that the increase in cell-cell contact, induced by microtubule depolymerization, requires signaling through a RhoA/Rho kinase pathway. The Rac-1 GTPase counteracts this pathway, because inhibition of Rac-1 signaling rapidly promotes epithelial barrier function, in a microtubule- and RhoA-independent fashion. Together, our data suggest that microtubule-RhoA-mediated signaling and Rac-1 control lung epithelial integrity through counteracting independent pathways.

scholarly journals TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2

2020 ◽  
Author(s):  
Yinfang Wang ◽  
Yingzhe Fan ◽  
Yitong Huang ◽  
Tao Du ◽  
Zongjun Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nk Cells ◽  
Interleukin 2 ◽  
A549 Cells ◽  
Endogenous Retrovirus ◽  
Alveolar Epithelial Cells ◽  
Cell Entry ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Ifn Γ

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous retrovirus latency and immune response, it is recently reported to be co-expressed with SARS-CoV-2 receptor in type II pneumocytes; however, the roles of TRIM28 in ACE2 expression and SARS-CoV-2 cell entry remain unclear. This study showed that knockdown of TRIM28 induces ACE2 expression and increases pseudotyped SARS-CoV-2 cell entry of A549 cells and primary pulmonary alveolar epithelial cells (PAEpiCs). In a co-culture model of NK cells and lung epithelial cells, our results demonstrated that NK cells inhibit TRIM28 and promote ACE2 expression in lung epithelial cells, which was partially reversed by depletion of interleukin-2 and blocking of granzyme B in the co-culture medium. Furthermore, TRIM28 knockdown enhanced interferon-γ (IFN-γ)-induced ACE2 expression through a mechanism involving upregulating IFN-γ receptor 2 (IFNGR2) in both A549 and PAEpiCs. Importantly, the upregulated ACE2 induced by TRIM28 knockdown and co-culture of NK cells was partially reversed by dexamethasone in A549 cells but not PAEpiCs. Our study identified TRIM28 as a novel regulator of ACE2 expression and SARS-CoV-2 cell entry.

The lack of attachment of transformed embryonic lung epithelial cells to collagen I is corrected by fibronectin and FXIII

1986 ◽  
Vol 86 (1) ◽  
pp. 95-107
Author(s):  
M. Paye ◽  
C.M. Lapiere
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Lung Epithelial Cells ◽  
Collagen I ◽  
Epithelial Cell Line ◽  
Embryonic Lung ◽  
Lung Epithelial ◽  
Minimal Concentration ◽  
Pulmonary Epithelial Cell

PER cells, a transformed pulmonary epithelial cell line that adhered to a large extent to a fibronectin substratum, were found to be attachment-deficient to collagen I. Although fibronectin can bind to collagen I monomers and polymers, the addition of exogenous fibronectin in the attachment medium induced the adhesion of these cells to collagen I polymers but not to monomers. By adding the transglutaminase of blood coagulation, FXIII, in the presence of fibronectin, the attachment of PER cells to collagen I monomers could be recovered while the minimal concentration of fibronectin needed to promote their adhesion to polymers was lowered. These studies indicate that FXIII enhances the fibronectin-mediated attachment of PER cells to collagen I.

scholarly journals Actomyosin-based Retrograde Flow of Microtubules in the Lamella of Migrating Epithelial Cells Influences Microtubule Dynamic Instability and Turnover and Is Associated with Microtubule Breakage and Treadmilling

1997 ◽  
Vol 139 (2) ◽  
pp. 417-434 ◽  
Author(s):  
Clare M. Waterman-Storer ◽  
E.D. Salmon
Keyword(s):  
Epithelial Cells ◽  
Dynamic Instability ◽  
Leading Edge ◽  
Unknown Origin ◽  
Time Lapse ◽  
Lung Epithelial Cells ◽  
Retrograde Flow ◽  
Microtubule Dynamic ◽  
Lung Epithelial ◽  
Time Lapse Imaging

We have discovered several novel features exhibited by microtubules (MTs) in migrating newt lung epithelial cells by time-lapse imaging of fluorescently labeled, microinjected tubulin. These cells exhibit leading edge ruffling and retrograde flow in the lamella and lamellipodia. The plus ends of lamella MTs persist in growth perpendicular to the leading edge until they reach the base of the lamellipodium, where they oscillate between short phases of growth and shortening. Occasionally “pioneering” MTs grow into the lamellipodium, where microtubule bending and reorientation parallel to the leading edge is associated with retrograde flow. MTs parallel to the leading edge exhibit significantly different dynamics from MTs perpendicular to the cell edge. Both parallel MTs and photoactivated fluorescent marks on perpendicular MTs move rearward at the 0.4 μm/min rate of retrograde flow in the lamella. MT rearward transport persists when MT dynamic instability is inhibited by 100-nM nocodazole but is blocked by inhibition of actomyosin by cytochalasin D or 2,3-butanedione–2-monoxime. Rearward flow appears to cause MT buckling and breaking in the lamella. 80% of free minus ends produced by breakage are stable; the others shorten and pause, leading to MT treadmilling. Free minus ends of unknown origin also depolymerize into the field of view at the lamella. Analysis of MT dynamics at the centrosome shows that these minus ends do not arise by centrosomal ejection and that ∼80% of the MTs in the lamella are not centrosome bound. We propose that actomyosin-based retrograde flow of MTs causes MT breakage, forming quasi-stable noncentrosomal MTs whose turnover is regulated primarily at their minus ends.

POTENTIATION OF FAS- AND TRAIL-MEDIATED APOPTOSIS BY IFN-γ IN A549 LUNG EPITHELIAL CELLS: ENHANCEMENT OF CASPASE-8 EXPRESSION THROUGH IFN-RESPONSE ELEMENT

Cytokine ◽  
2002 ◽  
Vol 20 (6) ◽  
pp. 283-288 ◽  
Author(s):  
Ki-Bae Kim ◽  
Yun-Hee Choi ◽  
In-Ki Kim ◽  
Chul-Woong Chung ◽  
Byung Ju Kim ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Caspase 8 ◽  
Response Element ◽  
Lung Epithelial ◽  
Ifn Γ ◽  
A549 Lung

scholarly journals Inhibition of acute lethal pulmonary inflammation by the IDO–AhR pathway

2017 ◽  
Vol 114 (29) ◽  
pp. E5881-E5890 ◽  
Author(s):  
Soung-Min Lee ◽  
Ha Young Park ◽  
Young-Sill Suh ◽  
Eun Hye Yoon ◽  
Juyang Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Pulmonary Inflammation ◽  
Lung Parenchyma ◽  
Lung Epithelial Cells ◽  
Dependent Manner ◽  
Independent Manner ◽  
Hematopoietic Stem ◽  
Lung Epithelial ◽  
Ifn Γ

The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4+ T cells transiently induced expression of indoleamine 2,3-dioxygenase (IDO) in lung parenchyma in an IFN-γ–dependent manner early after allogeneic hematopoietic stem cell transplantation (HSCT). Abrogation of host IDO expression by deletion of the IDO gene or the IFN-γ gene in donor T cells or by FK506 treatment resulted in acute lethal pulmonary inflammation known as idiopathic pneumonia syndrome (IPS). Interestingly, IL-6 strongly induced IDO expression in an IFN-γ–independent manner when deacetylation of STAT3 was inhibited. Accordingly, a histone deacetylase inhibitor (HDACi) could reduce IPS in the state where IFN-γ expression was suppressed by FK506. Finally, l-kynurenine produced by lung epithelial cells and alveolar macrophages during IPS progression suppresses the inflammatory activities of lung epithelial cells and CD4+ T cells through the aryl hydrocarbon receptor pathway. Taken together, our results reveal that IDO is a critical regulator of acute pulmonary inflammation and that regulation of IDO expression by HDACi may be a therapeutic approach for IPS after HSCT.

scholarly journals TACSTD2 upregulation is an early reaction to lung infection

2021 ◽  
Author(s):  
Sara Lenart ◽  
Peter Lenart ◽  
Hana Kotasova ◽  
Vendula Pelkova ◽  
Veronika Sedlakova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Physiological Role ◽  
Lung Epithelial Cells ◽  
Antibody Drug Conjugate ◽  
Epithelial Barrier Function ◽  
Transcriptomic Data ◽  
Transmembrane Glycoprotein ◽  
Lung Epithelial ◽  
Evolutionarily Conserved

TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. This increase may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.

scholarly journals Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1264
Author(s):  
Mitsutoshi Ishii ◽  
Tomoshi Tsuchiya ◽  
Ryoichiro Doi ◽  
Yoichi Morofuji ◽  
Takashi Fujimoto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Stromal Cells ◽  
Barrier Function ◽  
Lung Epithelial Cells ◽  
Gene Profiling ◽  
Cell Junctions ◽  
Cell Junction ◽  
Therapeutic Effects ◽  
Lung Epithelial

With the emergence of coronavirus disease-2019, researchers have gained interest in the therapeutic efficacy of mesenchymal stem/stromal cells (MSCs) in acute respiratory distress syndrome; however, the mechanisms of the therapeutic effects of MSCs are unclear. We have previously reported that adipose-derived MSCs (AD-MSCs) strengthen the barrier function of the pulmonary vessels in scaffold-based bioengineered rat lungs. In this study, we evaluated whether AD-MSCs could enhance the intercellular barrier function of lung epithelial cells in vitro using a transwell coculture system. Transepithelial electrical resistance (TEER) measurements revealed that the peak TEER value was significantly higher in the AD-MSC coculture group than in the AD-MSC non-coculture group. Similarly, the permeability coefficient was significantly decreased in the AD-MSC coculture group compared to that in the AD-MSC non-coculture group. Immunostaining of insert membranes showed that zonula occuldens-1 expression was significantly high at cell junctions in the AD-MSC coculture group. Moreover, cell junction-related gene profiling showed that the expression of some claudin genes, including claudin-4, was upregulated in the AD-MSC coculture group. Taken together, these results showed that AD-MSCs enhanced the barrier function between lung epithelial cells, suggesting that both direct adhesion and indirect paracrine effects strengthened the barrier function of lung alveolar epithelium in vitro.

IFN-γ Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage

2016 ◽  
Vol 36 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Chiou-Feng Lin ◽  
Shun-Yi Chien ◽  
Chia-Ling Chen ◽  
Chia-Yuan Hsieh ◽  
Po-Chun Tseng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Ifn Γ ◽  
Extracellular Trap ◽  
Trap Cell

scholarly journals Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip

2019 ◽  
Vol 7 ◽  
Author(s):  
Marcel Felder ◽  
Bettina Trueeb ◽  
Andreas Oliver Stucki ◽  
Sarah Borcard ◽  
Janick Daniel Stucki ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Impaired Wound Healing ◽  
Lung Epithelial
Sign in / Sign up

Export Citation Format

Share Document