Mucin 3 is involved in intestinal epithelial cell apoptosis viaN-(3-oxododecanoyl)-l-homoserine lactone-induced suppression of Akt phosphorylation

2014 ◽  
Vol 307 (2) ◽  
pp. C162-C168 ◽  
Author(s):  
Ryoko Taguchi ◽  
Shinya Tanaka ◽  
Ga-Hyun Joe ◽  
Hideaki Maseda ◽  
Nobuhiko Nomura ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Virulence Gene ◽  
Homoserine Lactone ◽  
Intestinal Epithelial ◽  
Cellular Functions ◽  
Virulence Gene Expression ◽  
Akt Phosphorylation ◽  
Epithelial Cell Apoptosis

N-acyl-homoserine lactones (AHL) are quorum-sensing molecules in bacteria that play important roles in regulating virulence gene expression in pathogens such as Pseudomonas aeruginosa. The present study compared responses between undifferentiated and differentiated Caco-2 cells to N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL). A low concentration of 3-oxo-C12-HSL (30 μM) is sufficient to reduce viability accompanied by apoptosis via the suppression of phosphorylation by Akt in undifferentiated Caco-2 cells. The suppression of Akt phosphorylation appears specific in 3-oxo-C12-HSL, because other AHLs did not influence the phosphorylation status of Akt. The reduced viability induced by 3-oxo-C12-HSL was partially recovered by constitutively active Akt overexpression in undifferentiated Caco-2 cells. Since mucin is considered a vital component of the gut barrier, we investigated whether mucin protects cellular functions induced by 3-oxo-C12-HSL in undifferentiated Caco-2 cells. The results showed that mucin protected undifferentiated Caco-2 cells from apoptosis induced by 3-oxo-C12-HSL. 3-Oxo-C12-HSL did not induce cell death in differentiated Caco-2 cells that expressed higher levels of mucin 3 (MUC3) than undifferentiated Caco-2 cells. In addition, 3-oxo-C12-HSL promoted cell death in undifferentiated Caco-2 cells transfected with MUC3 siRNA and reduced MUC3 expression in undifferentiated Caco-2 cells. Therefore, MUC3 might be responsible for the survival of undifferentiated intestinal epithelial cells in the presence of 3-oxo-C12-HSL through regulating Akt phosphorylation. In conclusion, 3-oxo-C12-HSL might influence the survival of undifferentiated intestinal epithelial cells as well as interactions between these cells and pathogens.

Efficacy of Plant-Derived Antimicrobials in Controlling Enterohemorrhagic Escherichia coli Virulence In Vitro

2016 ◽  
Vol 79 (11) ◽  
pp. 1965-1970 ◽  
Author(s):  
SANGEETHA ANANDA BASKARAN ◽  
ANUP KOLLANOOR-JOHNY ◽  
MEERA SURENDRAN NAIR ◽  
KUMAR VENKITANARAYANAN
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Antimicrobial Agents ◽  
Intestinal Epithelial Cells ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Cells ◽  
Intestinal Epithelial ◽  
Virulence Gene Expression ◽  
Human Intestinal Epithelial Cells

ABSTRACTEscherichia coli O157:H7 is a major foodborne pathogen that can cause serious human illness characterized by hemorrhagic diarrhea and kidney failure. The pathology of enterohemorrhagic E. coli O157:H7 (EHEC) infection is primarily mediated by verotoxins, which bind to the globotriaosylceramide receptor on host cells. Antibiotics are contraindicated for treating EHEC infection because they lead to increased verotoxin release, thereby increasing the risk of renal failure and death in patients. Thus, alternative strategies are needed for controlling EHEC infections in humans. This study investigated the effect of subinhibitory concentrations of five plant-derived antimicrobial agents (PDAs) that are generally considered as safe, i.e., trans-cinnamaldehyde, eugenol, carvacrol, thymol, and β-resorcylic acid, on EHEC motility, adhesion to human intestinal epithelial cells, verotoxin production, and virulence gene expression. All tested PDAs reduced EHEC motility and attachment to human intestinal epithelial cells (P < 0.05) and decreased verotoxin synthesis by EHEC. The reverse transcription real-time PCR data revealed that PDAs decreased the expression of critical virulence genes in EHEC (P < 0.05). The results collectively suggest that these PDAs could be used to reduce EHEC virulence, but follow-up studies in animal models are necessary to validate these findings.

Helicobacter hepaticusCytolethal Distending Toxin Causes Cell Death in Intestinal Epithelial Cells via Mitochondrial Apoptotic Pathway

Helicobacter ◽  
2010 ◽  
Vol 15 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Namal P. M. Liyanage ◽  
Karoline C. Manthey ◽  
Rohana P. Dassanayake ◽  
Charles A. Kuszynski ◽  
Gregory G. Oakley ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway

Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals

2007 ◽  
Vol 292 (1) ◽  
pp. G39-G52 ◽  
Author(s):  
Masahiro Iizuka ◽  
Kenji Sasaki ◽  
Yohei Hirai ◽  
Kenichi Shindo ◽  
Shiho Konno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Epithelial Cells ◽  
Egf Receptor ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

Epimorphin is a mesenchymal protein that regulates morphogenesis of epithelial cells. Our preliminary study suggested a novel function of epimorphin in enhancing survival of intestinal epithelial cells (IEC). Oxidative stress leads to cell injury and death and is suggested to be a key contributor to pathogenesis of inflammatory bowel disease. This study was conducted to determine whether epimorphin protects IEC from oxidative stress. Rat intestinal epithelial cell line IEC-6 was cultured with epimorphin (10 and 20 μg/ml), and the life span of IEC was assessed. The mean life span of IEC-6 cells was prolonged 1.9-fold ( P < 0.0006) by treatment with epimorphin. We then examined the epimorphin signaling pathways. Epimorphin phosphorylated epidermal growth factor (EGF) receptor, activated the MEK/extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and phosphatidylinositol 3 (PI3) kinase/Akt pathways, phosphorylated Bad, and induced Bcl-XL and survivin. Hydrogen peroxide (1 mM) induced cell death in 92% of IEC-6 cells, but epimorphin dramatically diminished (88.7%) cell death induced by hydrogen peroxide ( P < 0.0001). This protective effect of epimorphin was significantly attenuated by inhibitors of MEK and PI3 kinase ( P < 0.0001) or EGF receptor-neutralizing antibody ( P = 0.0007). In wound assays, the number of migrated cells in the wound area decreased (72.5%) by treatment with 30 μM hydrogen peroxide, but epimorphin increased the number of migrated cells 3.18-fold ( P < 0.0001). These results support a novel function of epimorphin in protecting IEC from oxidative stress. This anti-oxidative function of epimorphin is dramatic and is likely mediated by the activation of EGF receptors and the MEK/extracellular signal-regulated kinase and PI3 kinase/Akt signaling pathways and through the induction of anti-apoptotic factors.

scholarly journals Caspase-mediated cleavage of murine norovirus NS1/2 potentiates apoptosis and is required for persistent infection of intestinal epithelial cells

2018 ◽  
Author(s):  
Bridget A. Robinson ◽  
Jacob A. Van Winkle ◽  
Broc T McCune ◽  
A. Mack Peters ◽  
Timothy J. Nice
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Persistent Infection ◽  
Acute Gastroenteritis ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Murine Norovirus ◽  
Structural Protein ◽  
Human Norovirus ◽  
Caspase Cleavage

AbstractHuman norovirus (HNoV) is the leading cause of acute gastroenteritis and is spread by fecal shedding that can often persist for weeks to months after the resolution of symptoms. Elimination of persistent viral reservoirs has the potential to prevent outbreaks. Similar to HNoV, murine norovirus (MNV) is spread by persistent shedding in the feces and provides a tractable model to study molecular mechanisms of enteric persistence. Previous studies have identified non-structural protein 1 (NS1) from the persistent MNV strain CR6 as critical for persistent infection in intestinal epithelial cells (IECs), but its mechanism of action remains unclear. We now find that the function of CR6 NS1 is regulated by apoptotic caspase cleavage. Following induction of apoptosis in infected cells, caspases cleave the precursor NS1/2 protein, and this cleavage is prevented by mutation of caspase target motifs. These mutations profoundly compromise CR6 infection of IECs and persistence in the intestine. Conversely, NS1/2 cleavage is not required for acute replication in extra-intestinal tissues or in cultured myeloid cells, indicating an IEC-specific role. Intriguingly, we find that caspase cleavage of NS1/2 reciprocally promotes caspase activity, potentiates cell death, and amplifies spread among cultured IEC monolayers. Together, these data indicate that the function of CR6 NS1 is regulated by apoptotic caspases, and suggest that apoptotic cell death enables epithelial spread and persistent shedding.Author SummaryHuman Norovirus infection is highly contagious and the most common cause of acute gastroenteritis. Norovirus can be persistently shed after resolution of symptoms, perpetuating or initiating new outbreaks. Murine norovirus (MNV) is also persistently shed, enabling study of host and viral determinants of norovirus pathogenesis. We previously identified a critical role for MNV non-structural protein 1 (NS1), in persistence. Herein we find that regulation of NS1 by host apoptotic caspases is required for infection of intestinal epithelial cells, but not for extra-intestinal spread. Additionally, we demonstrate that NS1 reciprocally promotes cell death and spread among epithelial cells. These data identify regulation of NS1 by host proteases and suggest that apoptotic death is a determinant of epithelial spread and persistence.

scholarly journals Immunomodulatory Effects of TGF-β Family Signaling within Intestinal Epithelial Cells and Carcinomas

2019 ◽  
Vol 1 (2) ◽  
pp. 290-300
Author(s):  
Paula Marincola Smith ◽  
Anna Means ◽  
R. Beauchamp
Keyword(s):  
Epithelial Cells ◽  
Cytokine Production ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Immunomodulatory Effects ◽  
Cellular Functions ◽  
Epithelial Cancers ◽  
Causal Pathways

TGF-β superfamily signaling is responsible for many critical cellular functions including control of cell growth, cell proliferation, cell differentiation, and apoptosis. TGF-β appears to be critical in gastrulation, embryonic development, and morphogenesis, and it retains pleiotropic roles in many adult tissues and cell types in a highly context-dependent manner. While TGF-β signaling within leukocytes is known to have an immunosuppressive role, its immunomodulatory effects within epithelial cells and epithelial cancers is less well understood. Recent data has emerged that suggests TGF-β pathway signaling within epithelial cells may directly modulate pro-inflammatory chemokine/cytokine production and resultant leukocyte recruitment. This immunomodulation by epithelial TGF-β pathway signaling may directly impact tumorigenesis and tumor progression through modulation of the epithelial microenvironment, although causal pathways responsible for such an observation remain incompletely investigated. This review presents the published literature as it relates to the immunomodulatory effects of TGF-β family signaling within intestinal epithelial cells and carcinomas.

SDF-1/CXCL12 regulates cAMP production and ion transport in intestinal epithelial cells via CXCR4

2004 ◽  
Vol 286 (5) ◽  
pp. G844-G850 ◽  
Author(s):  
Michael B. Dwinell ◽  
Hiroyuki Ogawa ◽  
Kim E. Barrett ◽  
Martin F. Kagnoff
Keyword(s):  
Epithelial Cells ◽  
Ion Transport ◽  
Intestinal Epithelial Cells ◽  
Human Colon ◽  
Intestinal Epithelial ◽  
Camp Production ◽  
Cellular Functions ◽  
T84 Cells ◽  
Stromal Cell Derived Factor ◽  
Ht 29

Human colonic epithelial cells express CXCR4, the sole cognate receptor for the chemokine stromal cell-derived factor (SDF)-1/CXC chemokine ligand (CXCL) 12. The aim of this study was to define the mechanism and functional consequences of signaling intestinal epithelial cells through the CXCR4 chemokine receptor. CXCR4, but not SDF-1/CXCL12, was constitutively expressed by T84, HT-29, HT-29/-18C1, and Caco-2 human colon epithelial cell lines. Studies using T84 cells showed that CXCR4 was G protein-coupled in intestinal epithelial cells. Moreover, stimulation of T84 cells with SDF-1/CXCL12 inhibited cAMP production in response to the adenylyl cyclase activator forskolin, and this inhibition was abrogated by either anti-CXCR4 antibody or receptor desensitization. Studies with pertussis toxin suggested that SDF-1/CXCL12 activated negative regulation of cAMP production through Giα subunits coupled to CXCR4. Consistent with the inhibition of forskolin-stimulated cAMP production, SDF-1/CXCL12 also inhibited forskolin-induced ion transport in voltage-clamped polarized T84 cells. Taken together, these data indicate that epithelial CXCR4 can transduce functional signals in human intestinal epithelial cells that modulate important cAMP-mediated cellular functions.

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