scholarly journals The impact of oligosaccharide content, glycosidic linkages and lactose content of galacto-oligosaccharides (GOS) on the expression of mucus-related genes in goblet cells

2020 ◽  
Vol 11 (4) ◽  
pp. 3506-3515 ◽  
Author(s):  
Susana Figueroa-Lozano ◽  
Chengcheng Ren ◽  
Huifang Yin ◽  
Hien Pham ◽  
Sander van Leeuwen ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Direct Effect ◽  
Goblet Cell ◽  
Cell Function ◽  
Goblet Cells ◽  
The Impact

Galacto-oligosaccharides (GOS) are molecules known to impact goblet cell function and mucus composition. Our results show that their molecular structure have a direct effect on goblet cells and impact mucus synthesis-related genes.

scholarly journals Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
L. Contreras-Ruiz ◽  
A. Ghosh-Mitra ◽  
M. A. Shatos ◽  
D. A. Dartt ◽  
S. Masli
Keyword(s):  
Sjögren’S Syndrome ◽  
Inflammatory Cytokines ◽  
Goblet Cell ◽  
Ocular Surface ◽  
Cell Function ◽  
Sjögren's Syndrome ◽  
Goblet Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-αand IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

scholarly journals Benzalkonium Chloride-Preserved Anti-Glaucomatous Eye Drops and Their Effect on Human Conjunctival Goblet Cells in vitro

2021 ◽  
pp. 69-75
Author(s):  
Anne Hedengran ◽  
Xenia Begun ◽  
Olivia Müllertz ◽  
Zaynab Mouhammad ◽  
Rupali Vohra ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Survival ◽  
Goblet Cell ◽  
Benzalkonium Chloride ◽  
Goblet Cells ◽  
Eye Drops ◽  
Dependent Manner ◽  
The Impact ◽  
Conjunctival Goblet Cells

<b><i>Introduction:</i></b> Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. <b><i>Methods:</i></b> Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol<sup>®</sup> (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. <b><i>Results:</i></b> All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; <i>p</i> = 0.93), 71% for DS (0.0075% BAK; <i>p</i> = 0.067), 70% for OP (0.01% BAK; <i>p</i> = 0.054), and 69% for LT (0.02% BAK; <i>p</i> = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (<i>p</i> = 0.217), 52% for DS (<i>p</i> = 0.011), 34% for OP (<i>p</i> = 0.017), and 31% for LT (<i>p</i> = 0.0007). <b><i>Conclusion:</i></b> LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.

scholarly journals Bifidobacterium dentiumFortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Melinda A. Engevik ◽  
Berkley Luk ◽  
Alexandra L. Chang-Graham ◽  
Anne Hall ◽  
Beatrice Herrmann ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathways ◽  
Goblet Cell ◽  
Cell Function ◽  
Goblet Cells ◽  
Mucus Layer ◽  
Content Type ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

ABSTRACTMuch remains unknown about how the intestinal microbiome interfaces with the protective intestinal mucus layer.Bifidobacteriumspecies colonize the intestinal mucus layer and can modulate mucus production by goblet cells. However, selectBifidobacteriumstrains can also degrade protective glycans on mucin proteins. We hypothesized that the human-derived speciesBifidobacterium dentiumwould increase intestinal mucus synthesis and expulsion, without extensive degradation of mucin glycans.In silicodata revealed thatB. dentiumlacked the enzymes necessary to extensively degrade mucin glycans. This finding was confirmed by demonstrating thatB. dentiumcould not use naive mucin glycans as primary carbon sourcesin vitro. To examineB. dentiummucus modulationin vivo, Swiss Webster germfree mice were monoassociated with live or heat-killedB. dentium. LiveB. dentium-monoassociated mice exhibited increased colonic expression of goblet cell markersKrüppel-like factor 4(Klf4),Trefoil factor 3(Tff3),Relm-β,Muc2, and several glycosyltransferases compared to both heat-killedB. dentiumand germfree counterparts. Likewise, liveB. dentium-monoassociated colon had increased acidic mucin-filled goblet cells, as denoted by Periodic Acid-Schiff-Alcian Blue (PAS-AB) staining and MUC2 immunostaining.In vitro,B. dentium-secreted products, including acetate, were able to increase MUC2 levels in T84 cells. We also identified thatB. dentium-secreted products, such as γ-aminobutyric acid (GABA), stimulated autophagy-mediated calcium signaling and MUC2 release. This work illustrates thatB. dentiumis capable of enhancing the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways, with a net increase in mucin production.IMPORTANCEMicrobe-host interactions in the intestine occur along the mucus-covered epithelium. In the gastrointestinal tract, mucus is composed of glycan-covered proteins, or mucins, which are secreted by goblet cells to form a protective gel-like structure above the epithelium. Low levels of mucin or alterations in mucin glycans are associated with inflammation and colitis in mice and humans. Although current literature links microbes to the modulation of goblet cells and mucins, the molecular pathways involved are not yet fully understood. Using a combination of gnotobiotic mice and mucus-secreting cell lines, we have identified a human-derived microbe,Bifidobacterium dentium, which adheres to intestinal mucus and secretes metabolites that upregulate the major mucin MUC2 and modulate goblet cell function. Unlike otherBifidobacteriumspecies,B. dentiumdoes not extensively degrade mucin glycans and cannot grow on mucin alone. This work points to the potential of usingB. dentiumand similar mucin-friendly microbes as therapeutic agents for intestinal disorders with disruptions in the mucus barrier.

scholarly journals Type III interferon signaling restricts enterovirus 71 infection of goblet cells

2019 ◽  
Vol 5 (3) ◽  
pp. eaau4255 ◽  
Author(s):  
Charles Good ◽  
Alexandra I. Wells ◽  
Carolyn B. Coyne
Keyword(s):  
Goblet Cell ◽  
Intestinal Epithelium ◽  
Cell Function ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Goblet Cells ◽  
Neurological Complications ◽  
Ev71 Infection ◽  
Apical Surface ◽  
Type Iii

Recent worldwide outbreaks of enterovirus 71 (EV71) have caused major epidemics of hand, foot, and mouth disease with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but little is known about the mechanisms it uses to cross the human gastrointestinal tract. Using primary human intestinal epithelial monolayers, we show that EV71 infects the epithelium from the apical surface, where it preferentially infects goblet cells. We found that EV71 infection did not alter epithelial barrier function but did reduce the expression of goblet cell–derived mucins, suggesting that it alters goblet cell function. We also show that the intestinal epithelium responds to EV71 infection through the selective induction of type III interferons (IFNs), which restrict EV71 replication. Collectively, these findings define the early events associated with EV71 infections of the human intestinal epithelium and show that host IFN signaling controls replication in an IFN-specific manner.

scholarly journals Impact of P2X7 Purinoceptors on Goblet Cell Function: Implications for Dry Eye

2021 ◽  
Vol 22 (13) ◽  
pp. 6935
Author(s):  
Donald G. Puro
Keyword(s):  
Dry Eye ◽  
Goblet Cell ◽  
Cell Function ◽  
Tear Film ◽  
Goblet Cells ◽  
High Gain ◽  
High Temporal Resolution ◽  
Triggered Release ◽  
Voltage Gated Calcium Channels ◽  
Conjunctival Goblet Cells

By providing ~70% of the eye’s refractive power, the preocular tear film is essential for optimal vision. However, its integrity is often jeopardized by environmental and pathologic conditions that accelerate evaporation and cause sight-impairing dry eye. A key adaptive response to evaporation-induced tear film hyperosmolarity is the reflex-triggered release of tear-stabilizing mucin from conjunctival goblet cells. Here, we review progress in elucidating the roles of ion channels in mediating this important exocytotic response. Much is now known about the modulatory impact of ATP-sensitive potassium channels, nonspecific cation channels and voltage-gated calcium channels. Recently, we discovered that during unremitting extracellular hyperosmolarity, P2X7 receptor/channels also become activated and markedly impair goblet cell viability. However, our understanding of possible adaptive benefits of this P2X7 activation remains limited. In the present study, we utilized high-temporal resolution membrane capacitance measurements to monitor the exocytotic activity of single goblet cells located in freshly excised rat conjunctiva. We now report that activation of P2X7 purinoceptors boosts neural-evoked exocytosis and accelerates replenishment of mucin-filled granules after exocytotic depletion. Thus, P2X7 activation exerts a yin-yang effect on conjunctival goblet cells: the high-gain benefit of enhancing the supply of tear-stabilizing mucin is implemented at the high-risk of endangering goblet cell survival.

Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Zuojia Chen ◽  
Jialie Luo ◽  
Jian Li ◽  
Girak Kim ◽  
Eric S. Chen ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Goblet Cells ◽  
Short Chain Fatty Acids ◽  
Mucus Secretion ◽  
Intestinal Epithelial ◽  
Forkhead Box ◽  
Junction Proteins

Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.

scholarly journals Type III interferon signaling restricts Enterovirus 71 infection of goblet cells

2018 ◽  
Author(s):  
Charles Good ◽  
Alexandra I. Wells ◽  
Carolyn B. Coyne
Keyword(s):  
Goblet Cell ◽  
Intestinal Epithelium ◽  
Cell Function ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Goblet Cells ◽  
Neurological Complications ◽  
Ev71 Infection ◽  
Apical Surface ◽  
Type Iii

AbstractRecent worldwide outbreaks of enterovirus (EV71) have caused major epidemics of hand, foot, and mouth disease (HFMD) with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but very little is known about the mechanisms it utilizes to cross the human gastrointestinal (GI) tract. Using primary human intestinal epithelial monolayers, we show that EV71 infects the GI epithelium from the apical surface, where it preferentially infects goblet cells. Unlike echovirus 11 (E11), an enterovirus that infects enterocytes, EV71 infection did not alter epithelial barrier function, but did reduce the expression of a goblet cell-derived mucin, suggesting it alters goblet cell function. We also show that the intestinal epithelium responds to EV71 infection through the selective induction of type III IFNs, which potently restrict EV71 replication. Collectively, these findings define the early events associated with EV71 infections of the human intestinal epithelium and show that host IFN signaling controls replication in an IFN-specific manner.

Distinct epithelial responses in experimental colitis: implications for ion uptake and mucosal protection

2002 ◽  
Vol 283 (1) ◽  
pp. G169-G179 ◽  
Author(s):  
Ingrid B. Renes ◽  
Melissa Verburg ◽  
Daniëlle J. P. M. Van Nispen ◽  
Hans A. Büller ◽  
Jan Dekker ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Cell Function ◽  
Recovery Period ◽  
Disease Onset ◽  
Goblet Cells ◽  
Repair Capacity ◽  
Fatty Acid Binding ◽  
Expression Levels ◽  
Regenerative Phase ◽  
Active Disease

In the present study, we aimed to investigate enterocyte- and goblet cell-specific functions during the different phases of acute colitis induced with dextran sulfate sodium (DSS). Rats were treated with DSS for 7 days, followed by a 7-day recovery period. Colonic tissue was excised on days 2 (onset of disease), 7 (active disease), and 14(regenerative phase). Enterocyte functions were studied by the expression of carbonic anhydrases (CAs), sodium/hydrogen exchangers (NHEs) and intestinal fatty acid-binding protein (iFABP) and by alkaline phosphatase (AP) activity. The expression and secretion of the mucin Muc2 and trefoil factor family peptide-3 (TFF3) were used as parameters for goblet cell function. DSS induced a downregulation of the CAs, NHEs, and iFABP in some normal-appearing surface enterocytes and in most of the flattened-surface enterocytes during disease onset and active disease. During the regenerative phase most enterocytes expressed these genes again. Quantitative analysis revealed a significant decrease in CAs, NHEs, and iFABP expression levels during onset and active disease. During the regenerative phase, the expression levels of the CAs were restored, whereas the expression levels of the NHEs and iFABP remained decreased. In contrast, enterocyte-specific AP activity was maintained in normal and flattened enterocytes during DSS-induced colitis. Goblet cells continued to express MUC2 and TFF3 during and after DSS treatment. Moreover, Muc2 and TFF3 expression and secretion levels were maintained or even increased during each of the DSS-induced disease phases. In conclusion, DSS-induced colitis was associated with decreased expression of CAs, NHEs, and iFABP. The loss of these genes possibly accounts for some of the pathology seen in colitis. The maintenance or upregulation of Muc2 and TFF3 synthesis and secretion levels implies that goblet cells at least maintain their epithelial defense and repair capacity during acute inflammation induced by DSS.

scholarly journals Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity

2021 ◽  
Author(s):  
Hassan Melhem ◽  
Berna Kaya ◽  
Tanay Kaymak ◽  
Philipp Wuggenig ◽  
Emilio Flint ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Goblet Cell ◽  
Cell Function ◽  
Critical Role ◽  
Goblet Cells ◽  
Mucosal Barrier ◽  
Critical Element ◽  
Citrobacter Rodentium ◽  
Invasive Bacterial Infection ◽  
Genetic Deletion

Goblet cells are essential for maintaining intestinal health and for the defense against invasive bacterial infection. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. Here we found that epithelial Gpr35 plays a critical role in goblet cell function. Genetic deletion of Gpr35 in epithelial cells but not in from macrophages results in goblet cell depletion and dysbiosis, rendering these mice more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows how the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota.

scholarly journals Modulation of Intestinal Goblet Cell Function during Infection by an Attaching and Effacing Bacterial Pathogen

2007 ◽  
Vol 76 (2) ◽  
pp. 796-811 ◽  
Author(s):  
Kirk S. B. Bergstrom ◽  
Julian A. Guttman ◽  
Mohammad Rumi ◽  
Caixia Ma ◽  
Saied Bouzari ◽  
...  
Keyword(s):  
Immune System ◽  
Goblet Cell ◽  
Cell Function ◽  
Bacterial Pathogen ◽  
Goblet Cells ◽  
Cell Depletion ◽  
Intestinal Lumen ◽  
Host Immune System ◽  
Immunocompetent Mice

ABSTRACT The attaching and effacing (A/E) bacterial pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli and the related mouse pathogen Citrobacter rodentium colonize their hosts' intestines by infecting the apical surfaces of enterocytes, subverting their function, and they ultimately cause diarrhea. Surprisingly, little is known about the interactions of these organisms with goblet cells, which are specialized epithelial cells that secrete the protective molecules Muc2 and trefoil factor 3 (Tff3) into the intestinal lumen. C. rodentium infection leads to dramatic goblet cell depletion within the infected colon, yet it is not clear whether C. rodentium infects goblet cells or if this pathology is pathogen or host mediated. As determined by immunostaining and PCR, both the number of goblet cells and the expression of genes encoding Muc2 and Tff3 were significantly reduced by day 10 postinfection. While electron microscopy and immunostaining revealed that C. rodentium directly infected a fraction of colonic goblet cells, C. rodentium localization did not correlate with goblet cell depletion. To assess the role of the host immune system in these changes, Rag1 knockout (KO) (T- and B-cell-deficient) mice were infected with C. rodentium. Rag1 KO mice did not exhibit the reduction in the number of goblet cells or in mediator (Muc2 and Tff3) expression observed in infected immunocompetent mice. However, reconstitution of Rag1 KO mice with T and B lymphocytes from C57BL/6 mice restored the goblet cell depletion phenotype during C. rodentium infection. In conclusion, these studies demonstrated that while colonic goblet cells can be subject to direct infection and potential subversion by A/E pathogens in vivo, it is the host immune system that primarily modulates the function of these cells during infection.

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