{"title":"Interactions between the Bronchial Epithelium and Fibrocytes in the Pathogenesis of Airway Remodeling in Asthma","authors":"A. Bellini, Matthias Schmidt, S. Mattoli","doi":"10.2174/1875044301306010001","DOIUrl":"https://doi.org/10.2174/1875044301306010001","url":null,"abstract":"The histopathologic features of asthma include chronic airway inflammation, increased density of fibroblasts and myofibroblasts in the lamina propria and presence of structural abnormalities of the bronchial wall collectively re- ferred to with the term \"airway remodeling\". The newly emerged population of fibroblasts and myofibroblasts contributes to airway remodeling by producing excessive amounts of collagenous and non-collagenous extracellular matrix compo- nents in the subepithelial zone and by expanding the mass of contractile cells in the bronchial wall. A substantial propor- tion of these mesenchymal cells in asthma exhibit the phenotypic and functional characteristic of fibrocytes, which repre- sent a unique population of bone marrow-derived mesenchymal progenitors recruited to tissue sites from the circulation in response to injury or in chronic inflammatory conditions. Recent studies have demonstrated that the asthmatic bronchial epithelium is a major source of fibrocyte chemoattractants and growth factors. This review will focus on the novel obser- vations suggesting that asthmatic epithelial cells may play a key role in the development and progression of airway re- modeling by promoting the recruitment and local differentiation of fibrocytes.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"6 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2013-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68111130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Micropatterning Co-cultures of Epithelial Cells on Filter Insert Substrates","authors":"Ana C. Paz, Sahar Javaherian, A. McGuigan","doi":"10.2174/1875044301205010077","DOIUrl":"https://doi.org/10.2174/1875044301205010077","url":null,"abstract":"A key feature of mature epithelium is the presence of an apical-basal polarization. In vitro this is achieved by culturing either pure populations of epithelial cells or unorganized mixtures of primary cell populations harvested from epithelial tissues in a filter insert culture system. In addition to epithelial cells however, multiple other cell types are also present in normal epithelium in a specific organization. Generally the organization of component cells within a tissue is critical for normal function. The importance of the organization of different cell populations within normal and diseased epithelium in vitro has received little attention, in part due to the lack of available methods for spatially controlling multiple cell populations while maintaining the culture conditions necessary to generate polarized and mature epithelium. We have developed a set of micropatterning techniques to spatially control the organization of co-cultures of epithelial cells on filter insert membranes under the culture conditions necessary to induce epithelial cell polarization. We describe a fibronectin microprinting method that allows arbitrary pattern generation and a parafilm insert method that allows only simple stripe geometry patterning but does not require the photolithographic equipment that the fibronectin microprinting method requires, and can be adopted by any epithelial biology lab. We also demonstrate that our micropatterning methods do not alter the formation of cilia, a marker of epithelium maturation. Our methods provide a novel tool for studying epithelial biology in polarized epithelial sheets containing multiple cell populations with controlled organization.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"77-85"},"PeriodicalIF":0.0,"publicationDate":"2012-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68111123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial - Augmenting Epithelial Barrier Function","authors":"J. M. Mullin","doi":"10.2174/1875044301205010010","DOIUrl":"https://doi.org/10.2174/1875044301205010010","url":null,"abstract":"The simplest multicellular animal organisms, coelenterates, are essentially floating intestines in the sea. More fundamentally, they are ‘barrier tubes’ that attempt to compartmentalize the environment they exist in. It is said that ontogeny recapitulates phylogeny. It is thus interesting that the blastocyst, among the earliest multicellular embryonic structures, is essentially a sac comprised of polarizing cells. Like the coelenterate, it is also compartmentalizing the environment that it exists in, creating an internal fluid compartment distinct from an external one. So on both an evolutionary basis and a developmental basis, the singular importance of fluid compartmentation and barrier cell linings was a concept that nature apparently grabbed hold of with both hands and never let go, as it kept ramifying the theme. The human body is in a sense a manifold of many different sacs and tubes: a respiratory tract, a GI tract, a urinary tract, the skin, a reproductive tract, a vasculature, a central nervous system encased in a medium (cerebrospinal fluid) quite distinct from blood. We are intimately and fundamentally divided into luminal and abluminal compartments.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"10-12"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancement of Epithelial Barrier Function by Probiotics","authors":"K. Madsen","doi":"10.2174/1875044301205010055","DOIUrl":"https://doi.org/10.2174/1875044301205010055","url":null,"abstract":"Probiotics are microbial organisms that are administered in supplements or foods to enhance the well-being of the host. There exists substantial evidence that in a strain and dose-dependent manner, probiotics can modulate systemic and mucosal immune function, improve intestinal barrier function, alter gut microecology, and exert metabolic effects on the host. Several strains of Lactobacillus and Bifidobacterium are able to compete with pathogens for binding to intestinal epithelial cells, and can displace pathogens. Epithelial cell signalling pathways are stimulated by whole microbes, structural components, and microbial-produced metabolites. In particular, the NF-kB pathway is modulated by probiotics at many different levels with effects seen on IB degradation and ubiquitination, proteasome function, and nuclear- cytoplasmic movement of RelA through a PPAR-gamma dependent pathway. In a strain and dose-dependent manner, probiotic strains have been shown to alter tight junction protein expression and/or localization in both in vivo and in vitro models. Probiotics can also enhance gut barrier function via increased production of cytoprotective molecules such as heat-shock proteins. In addition, probiotics are able to prevent cytokine- and oxidant-induced epithelial damage by promoting cell survival. Lactobacillus GG and soluble factors (p75 and p40) released from LGG prevented epithelial cell apoptosis through activating anti-apoptotic Akt in a phosphatidylinositol-3'-kinase (PI3K)-dependent manner and inhibiting pro-apoptotic p38/MAPK activation. It is clear that host-microbial interactions at the gut mucosal surface are critical for health and overall homeostasis and probiotics may possibly be harnessed to enhance barrier function in order to maintain health and protect against disease.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"55-59"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68111037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Zinc and Hepatocyte Nuclear Factor-4 in Alcohol-Induced Intestinal Barrier Dysfunction","authors":"Zhanxiang Zhou, Wei Zhong","doi":"10.2174/1875044301205010019","DOIUrl":"https://doi.org/10.2174/1875044301205010019","url":null,"abstract":"Zinc is an essential micronutrient and plays an important role in maintaining intestinal epithelial integrity. Increasing evidence support that zinc homeostasis has significant impact on the intestinal barrier via regulation of epithelial tight junction proteins. Intestinal barrier plays a critical role in the prevention of endotoxin penetration from the intestinal lumen to the blood. Disruption of the intestinal barrier leads to elevation of blood endotoxin level, namely endotoxemia. Endotoxemia may lead to proinflammatory cytokine production and inflammation, thereby being an etiological factor in the pathogenesis of alcoholic liver disease (ALD). Recent studies demonstrated that oxidative stress and zinc deficiency correlate well with alcohol-induced gut leakiness. Alcohol exposure induces oxidative stress which, in turn, releases zinc from proteins. Hepatocyte nuclear factor-4 (HNF-4 ) is a zinc finger transcription factor which abundantly distributes in the intestine, particularly the distal intestine. Inactivation of HNF-4 correlates well with alcohol-induced down- regulation of tight junction proteins. This review discusses mechanisms involved in alcohol-induced intestinal epithelial barrier disruption with emphasis on the relationship among oxidative stress, zinc deficiency, and HNF-4 inactivation.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role for the Bacterial Signal Indole in Promoting Epithelial Cell Barrier Function","authors":"T. Bansal, R. Alaniz, A. Jayaraman","doi":"10.2174/1875044301205010032","DOIUrl":"https://doi.org/10.2174/1875044301205010032","url":null,"abstract":"Interkingdom (IK) signaling, in which pathogenic bacteria recognize human hormones in the gastrointestinal tract to initiate infection, has recently emerged as an important contributor to gastrointestinal tract infections. While a majority of studies have primarily focused on the effect of host molecules on pathogens, recent work from our lab has demonstrated that human intestinal epithelial cells can also recognize bacterial signaling molecules. We demonstrated that indole, secreted to ~ 500 � M by commensal Escherichia coli, increased expression of tight junction proteins and genes involved in mucin production in HCT-8 intestinal epithelial cells, thus enhancing their barrier properties. These results were consistent with an observed increased in trans-epithelial resistance on exposure to indole over 24 h. Since indole is structurally similar to melatonin, and melatonin is a hormone that regulates the dark-cycle in the eye, we also investigated role of indole on human retinal pigment epithelium (RPE) cells. Our data show that indole increases trans-epithelial resistance of RPE cells, and attenuated their proliferation and migration. Our results suggest a beneficial role for indole in the treatment of eye diseases, and are discussed in detail in this article.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"32-38"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Somrudee Chuenkitiyanon, N. Vardhanabhuti, S. Jianmongkol
{"title":"A Potential Benefit of Quercetin in Preserving Tight Junction Integrity","authors":"Somrudee Chuenkitiyanon, N. Vardhanabhuti, S. Jianmongkol","doi":"10.2174/1875044301205010028","DOIUrl":"https://doi.org/10.2174/1875044301205010028","url":null,"abstract":"Disruption of tight junction (TJ) integrity can occur from loss of TJ protein expression and/or disorganization. Consequently, epithelial/endothelial barriers lose their barrier functions in the control over paracellular transport, leading to the compromised defense mechanism of the organ. The TJ disruption has been related to multiple signal transduction pathways including mitogen-activated protein kinases (MAPK). Quercetin is one of the most widely studied flavonoids with broad spectrum of pharmacological activities. In addition to antioxidant capability, quercetin may exert its actions via the alteration of protein kinase activities and the sequential signaling processes. This may enable quercetin to prevent the disintegration of TJ structure and to enhance the expression, localization and interaction of TJ proteins. This review presents the information to corroborate the potential benefit of quercetin in preserving integrity and function of TJ complexes. The involvement of protein kinase C (PKC) and MAPK signaling pathway is emphasized.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"28-31"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methionine Restriction and Modification of Epithelial Tight Junction Barrier Function and Permeability","authors":"Xuexuan Wang, J. M. Mullin","doi":"10.2174/1875044301205010039","DOIUrl":"https://doi.org/10.2174/1875044301205010039","url":null,"abstract":"It is well known that caloric restriction leads to an increased longevity by forestalling age-related diseases. Dietary restriction of methionine also renders similar benefits. In this review, we report studies on the effect of methionine restriction on epithelial barrier function in a renal epithelial LLC-PK1 cell, a rodent gastrointestinal model and a clinical trial using Crohn's patients. In LLC-PK1 cell culture, a reduction of culture medium methionine by 80% resulted in altered tight junctional claudin composition with improved epithelial barrier function as exemplified by increased trans- epithelial electrical resistance and decreased paracellular leak to 14 C-D-mannitol. In addition to small but significant reductions in plasma and intracellular colonocyte methionine levels, dietary methionine restriction tightens intestinal epithelium and reduces mannitol permeability in rat colonic, but not ileal tissue. Crohn's patients on methionine-restricted diet reported improved symptoms as demonstrated by a reduced CDAI index, but this diet was not able to significantly reduce the plasma methionine level in patients recruited. An increased urinary lactulose/mannitol ratio was also the result of the regimen in Crohn's patients, suggesting an increased, rather than decreased ileal leakage. Overall, our results showed that reduction in dietary intake of methionine is promising in improving at least some epithelial barriers and this may be through altering tight junctional protein compositions. Methionine restriction might result in contrasting effects depending on the tissue type and possible disease conditions, thus wider range of studies are required.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"39-46"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68111026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Slattery, Natalia Martín-Martín, T. McMorrow, M. Ryan
{"title":"Enhancement of Renal Tubular Epithelial Cell Barrier Function by the Immunosuppressant Drugs Cyclosporine A and Sirolimus","authors":"C. Slattery, Natalia Martín-Martín, T. McMorrow, M. Ryan","doi":"10.2174/1875044301205010060","DOIUrl":"https://doi.org/10.2174/1875044301205010060","url":null,"abstract":"The primary function of the kidney includes the elimination of waste products and the maintenance of fluid and electrolyte composition of the body. The functioning unit of the kidney is the nephron including the glomerulus with a filtration function and the tubule with a reabsorption and secretion function. The fluid and electrolyte homeostasis is achieved largely through selective, vectorial transport facilitated by the renal tubular epithelium. This involves both trans- cellular and paracellular transport. Paracellular transport across renal tubular epithelial tight junctions (TJs) varies in dif- ferent parts of the nephron. The relative concentrations of different claudins that are located in the TJ at any time deter- mine the ion and size selectivity of the paracellular diffusion pathway in the kidney as in other tissues. In this article, we review work from our own laboratory and others providing evidence that immunosuppressive drugs, especially cyclosporine A (CsA) and sirolimus (SRL) and can alter transport molecules in kidney tubules. We outline evidence that CsA and SRL can enhance renal epithelial barrier function as indicated by transepithelial electrical resistance (TEER). The possible signalling mechanisms involved in altering the TJs and claudins by CsA and SRL are outlined and involve both TGF- 1 and the ERK 1/2. These effects of CsA and SRL on kidney epithelia cell barrier function may help to explain some of the renal transport defects and nephrotoxicity seen with CsA and SRL. However if similar effects occur systemically in vivo, with these two immunosuppressive drugs, the enhancement of barrier function in areas of the body may decrease luminal antigen presentation, decreasing immune activation and support the immunosuppressive action of these drugs.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"60-66"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68111117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher P. Farrell, M. Barr, J. M. Mullin, L. Lande, M. Zitin
{"title":"Epithelial Barrier Leak in Gastrointestinal Disease and Multiorgan Failure","authors":"Christopher P. Farrell, M. Barr, J. M. Mullin, L. Lande, M. Zitin","doi":"10.2174/1875044301205010013","DOIUrl":"https://doi.org/10.2174/1875044301205010013","url":null,"abstract":"There are a myriad of clinical conditions whose disease etiology involves leakiness of an epithelial and/or endothelial barrier. To underscore the medical usefulness of agents that can augment barrier function, the theme of this special issue, two disease areas are highlighted. The first is the phenomenon of \"leaky gut\" which can play relatively obvious roles in gastrointestinal diseases such as celiac disease, Crohn's disease, and ulcerative colitis. It may play less obvious roles in seemingly unrelated illnesses such as autism, diabetes and certain microbial infectious diseases. A second disease area where barrier compromise plays a major role is multi-organ failure, a major cause of death in ICUs. Multi-organ failure highlights the important effect that the immune system and oxidative stress can have on barrier elements. The use of barrier enhancing and protecting agents in nutritional feeding in ICUs should be an area of intense interest in the future. Keyword: Tight junctions, inflammatory bowel disease, multiorgan dysfunction syndrome.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"5 1","pages":"13-18"},"PeriodicalIF":0.0,"publicationDate":"2012-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}