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PubMed2003

Tyrosine phosphorylation of occludin attenuates its interactions with ZO-1, ZO-2, and ZO-3.

Occludin, the transmembrane integral protein of the tight junction, plays a crucial role in the molecular organization and function of tight junction. While the homotypic interaction of extracellular loops of occludin appears to determine the barrier function of tight junction, the intracellular C-terminal tail, C-occludin, interacts with other tight junction proteins such as ZO-1, ZO-2, and ZO-3 and with the actin filaments of cytoskeleton. In the present study we phosphorylated GST-fused C-occludin on tyrosine residues, in TKX1 Epicurian coli or by active c-Src in vitro. c-Src binds to occludin and phosphorylates it on tyrosine residues. The effect of tyrosine phosphorylation of C-occludin on its ability to bind ZO-1, ZO-2, ZO-3, and F-actin was evaluated. Results show that the amounts of ZO-1, ZO-2, and ZO-3 bound to tyrosine phosphorylated C-occludin were several fold less than the amounts bound to non-phosphorylated C-occludin. However, the amount of tyrosine phosphorylated C-occludin bound to F-actin was not significantly different from the amount of non-phosphorylated C-occludin bound to F-actin. These results demonstrate that tyrosine phosphorylation of occludin reduces its ability to bind ZO-1, ZO-2, and ZO-3, but not F-actin. Results also suggest that c-Src-mediated disruption of tight junction may involve tyrosine phosphorylation of occludin.

Actins↗
PubMed1993

Biogenesis of structural intercellular junctions during cleavage in the mouse embryo.

The preimplantation embryo differentiates the trophectoderm epithelium which, from the 32-cell stage, generates the blastocoel of the blastocyst and, after implantation, gives rise to most extraembryonic lineages of the conceptus. Trophectoderm differentiation begins at compaction (8-cell stage) when cell-cell adhesion, mediated by uvomorulin, and epithelial cell polarisation first occur. Here, we review our work on the biogenesis of tight junctions and desmosomes during epithelial differentiation. Tight junction construction begins at compaction and appears to be a gradual process, both at morphological and molecular levels. This maturation pattern may be due in part to sequential expression of tight junction constituents from the embryonic genome. Tight junction formation is dependent upon uvomorulin adhesion but can be inhibited by different means without apparently disturbing cell adhesion or polarisation. Cell interactions appear to regulate tight junction tissue specificity, in part by controlling the level of synthesis of constituents. Desmosome formation begins at the 32-cell stage, particularly as the embryo initiates blastocoel accumulation, and, in contrast with tight junction formation, does not appear to be a gradual process. Thus, nascent desmosomes appear mature in terms of their molecular composition. Desmosomal proteins are synthesised well in advance of desmosome formation but the synthesis of the principal glycoprotein components begins at the blastocyst stage and may regulate the timing of junction assembly. Implications of these differing patterns of biogenesis for the embryo are discussed.

Animals↗
PubMed2000

Immunohistochemical study of tight junction-related protein in neovasculature in astrocytic tumor.

To clarify whether the neovasculature of brain tumors preserves blood-brain barrier (BBB) functions, we studied the expression of a tight junction-related protein, Zo-1, using immunohistochemistry. Twenty-six astrocytic tumors were examined using an anti-Zo-1 Mab, and Zo-1 expression was compared with the expression of vasicular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) (fit-1), and antiproliferative cell nuclear antigen (PCNA). A positive reaction for Zo-1 was seen in the endothelial cells in micro-blood vessels in all astrocytic tumors. The reactions for Zo-1 in the endothelial cells forming glomeruloid proliferations in newly formed micro-blood vessels in high-grade tumors were weaker than those in the endothelial cells of normal cerebral capillaries. Although there is a negative correlation between positive immunoreactions for BBB-related proteins and the expression of VEGF of the endothelial cells in micro-blood vessels, the proliferative activity of tumor cells, and histological grades, the present findings suggest that the endothelial cells of the neovasculature of high-grade tumors preserve partial BBB function at the cellular level. Because of the ease of immunohistochemical procedures compared with electron microscopic examination, the immunohistochemical detection of Zo-1 should provide a useful marker for tight junctions.

Adolescent↗
PubMed1988

[Architectural ultrastructure of the urinary bladder epithelium. II. Changes in the urine-blood barrier in the contracted and distended state in the normal and inflammatory bladder].

The urinary bladder epithelium in mammals, including humans, has a low permeability to ions and small molecules such as sodium, urea and water. Two structures, asymmetrical luminal plasma membrane and tight junction between superficial cells, have been said responsible for the urine-blood barrier. The permeability of junctional complex between superficial cells to lanthanum was observed in rat urinary bladder epithelium by transmission electron microscopy (TEM). In the normal bladder epithelium, confirmed by bacteriological examination, most junctions between superficial cells are the tight junctions and 1 to 9% of the junctions are leaky. The lanthanum, known to penetrate the leaky junctions, is demonstrated in the intercellular space between intermediate and basal cells. This suggests that desmosomes between these cells have no barrier function. In the experimentally inflammatory bladder epithelium all junctions are tight and no leaky junction is found between superficial cells. In contrast, if the superficial cells were stripped off in the inflammatory change, the lanthanum penetrates the junction between denuded intermediate cells. In the normal bladder epithelium the structural junctions between superficial cells have no changes during contraction and distension. Thus this suggests that the permeability to lanthanum does not change during contraction and distension.

Animals↗
PubMed1984

Tubulocisternal endoplasmic reticulum in human eccrine sweat glands.

Human eccrine sweat glands, including those expressing the gene for cystic fibrosis, were stained sequentially en bloc with uranyl acetate, lead citrate and copper sulfate, and osmium tetroxide for the ultrastructural demonstration of tubulocisternal endoplasmic reticulum (TER). This organelle has been associated with water and electrolyte transport in other epithelia. TER was present in the apical cytoplasm and basolateral cytoplasm circumscribing intercellular canaliculi of clear cells in the secretory coil and in the apical cuticular cytoplasm of luminal cells in the coiled duct. In both the secretory coil and duct, TER was situated strategically around the tight junctions. Together, the TER and tight junctions may regulate the secretory and absorptive permeability of the eccrine sweat gland to NaCl and water. The dark cell of the coil which is exocrine, and the deep cell of the duct which lacked tight junctions, did not contain TER. In sweat glands obtained from three cases of cystic fibrosis, elements of TER were more prevalent and complex in luminal cells of the secretory duct than was the TER in normal sweat glands. This difference may be a consequence of the basic electrolyte abnormality of cystic fibrosis.

Cystic Fibrosis↗
PubMed2003

The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity.

Tight junctions play a central role in the establishment of cell polarity in vertebrate endothelial and epithelial cells. A ternary protein complex consisting of the cell polarity proteins PAR-3 and PAR-6 and the atypical protein kinase C localizes at tight junctions and is crucial for tight junction formation. We have recently shown that PAR-3 directly associates with the junctional adhesion molecule (JAM), which suggests that the ternary complex is targeted to tight junctions of epithelial cells through PAR-3 binding to JAM. The expression of JAM-related proteins by endothelial cells prompted us to test whether recruitment of the ternary complex in endothelial cells can occur through binding to JAM-2, JAM-3, endothelial cell-selective adhesion molecule (ESAM) or coxsackie- and adenovirus receptor (CAR). Here we show that the two JAM-related proteins JAM-2 and JAM-3 directly associate with PAR-3. The association between PAR-3 and JAM-2/-3 is mediated through the first PDZ domain of PAR-3. In agreement with the predominant expression of JAM-2 and JAM-3 in endothelial cells, we found that PAR-3 is expressed by endothelial cells in vivo and is localized at cell contacts of cultured endothelial cells. PAR-3 associates with JAM-2/-3 but not with the JAM-related Ig-superfamily members ESAM or CAR. In addition, we show that the tight junction-associated protein ZO-1 associates with JAM-2/-3 in a PDZ domain-dependent manner. Using ectopic expression of JAM-2 in CHO cells, we show that the junctional localization of JAM-2 is regulated by serine phosphorylation and that its clustering at cell-cell contacts recruits endogenous PAR-3 and ZO-1. Our findings suggest that JAM-2 affects endothelial cell junctions by its regulated clustering at intercellular contacts, and they support a role for JAM-2, and possibly JAM-3, in tight junction formation of endothelial cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Show me the pathway! Regulation of paracellular permeability by Na(+)-glucose cotransport.

The physiological impact of Na(+)-nutrient cotransport-dependent regulation of intestinal tight junction permeability has been controversial. Nonetheless, increased permeability of small intestinal mucosae and enterocyte tight junctions as a consequence of Na(+)-nutrient cotransport has been documented by a significant number of in vivo and in vitro studies. Some details of the intracellular signaling events that regulate this process have been described recently. The aims of this article are to: (i) review studies of tight junction regulation and paracellular nutrient absorption in mammalian intestine, (ii) identify potential applications of tight junction regulation, and (iii) summarize recent progress in defining molecular mechanisms that lead to altered tight junction permeability.

Absorption↗
PubMed1976

Intercellular junctions in the reticular lamina of the organ of Corti.

Junctions between the cells in the reticular lamina of the organ of Corti were examined in thin sections and after freeze-fracturing to find a structural basis for the large ionic differences between the endolymph and perilymph. The apices of the cells in the reticular lamina are joined by a band of tight junctions spaced at 140 A intervals. Beneath this apical band the organization of the tight junctions depends on whether they join a supporting cell and a hair cell, or two supporting cells. At hair cell junctions with supporting cells, there is an extensive labyrinth of tight junctions enclosing lengthy, tortuous passages whose walls are composed of either multiple parallel or single junctions. At appositions between two supportinc cells, maculae or fasciae occludentes lie immediately beneath the apical bands of closely spaced tight junctions, near the top of the zonulae adherentia which are characteristic of appositions between supporting cells. The complexes of tight junctions, or zonulae occludentes, between extralaminar supporting cells differ from those in the reticular lamina. The extralaminar cells are joined by a band of four to seven branching, anastomotic tight junctions. Thus, these junctions are like zonulae occludentes in other tissues. The novel organizations of the tight junctions in the reticular lamina, different from those between the extralaminar supporting cells, suggests a special role for these junctions in the reticular lamina. Two sizes of gap junctions link, and presumably couple, supporting cells in the reticular lamina.

Animals↗
PubMed2004

Inhibition of MAP kinase activity moderates changes in expression and function of Cx32 but not claudin-1 during DNA synthesis in primary cultures of rat hepatocytes.

The signal transduction pathways and activation of the MAP kinase or PI3 kinase signaling cascade regulate a variety of cellular processes, including proliferation and differentiation in hepatocytes. To elucidate the mechanisms of signal transmission required for the regulation of gap and tight junctions during DNA synthesis in rat hepatocytes, we determined changes of expression and function of gap and tight junctions of cells grown in primary culture, using inhibitors of signaling pathways for MAP kinase (PD98059) and PI3 kinase (LY294002). During the stimulation of DNA synthesis induced by epidermal growth factor (EGF), immunoreactivity and mRNAs of gap junction protein Cx32 and of tight junction protein claudin-1 markedly decreased with reduction of gap junctional intercellular communication (GJIC) and the fence function of tight junctions. In Western blots, whole-cell lysate of claudin-1 protein decreased and phosphorylated Cx32 protein in the insoluble fraction of Triton X-100 increased during the stimulation of DNA synthesis. During reinhibition of DNA synthesis, the changes of Cx32 and claudin-1 returned to control levels, as did both functions. In treatment with the inhibitors before DNA synthesis, PD98059 inhibited the changes of expression and function of Cx32, but not claudin-1, without inhibition of cell growth, whereas LY294002 completely inhibited cell growth. These findings indicate that the PI3 kinase pathway rather than the MAP kinase pathway plays an important role for EGF-induced proliferation of rat hepatocytes, and that changes of Cx32 in hepatocytes during the stimulation of DNA synthesis may be in part controlled through MAP kinase. Furthermore, Cx32, but not claudin-1, protein may be a target of activated MAP kinase in hepatocytes.

Animals↗
PubMed2001

Occludin expression in microvessels of neoplastic and non-neoplastic human brain.

The tight junction protein occludin 'glues' normal, adjacent brain microvessel endothelial cells together. Malignant brain tumours cause cerebral oedema because they have leaky endothelial tight junctions, which allow plasma fluid to enter the brain from the microvessel lumen. In order to identify molecular abnormalities in tumour endothelial tight junctions, we investigated occludin expression in microvessels from adult human non-neoplastic brain tissue using immunohistochemistry and immunoblotting. The proportions of microvessels immunolabelling for occludin were >2/3 in 5/5 non-neoplastic brain tissue samples, >1/3 in 5/5 low grade (Daumas-Duport I or II) astrocytomas and <1/3 in 5/5 high grade (III or IV) astrocytomas and 6/6 metastatic adenocarcinomas. Six non-neoplastic brain tissue immunoblots gave a 55-kDa occludin band, three low-grade astrocytomas gave 55-kDa and 60-kDa bands, 13 high-grade astrocytomas gave 60-kDa or no band and four adenocarcinomas did not give an occludin band. Expression of 55-kDa occludin inversely correlated with the presence of contrast enhancement on computed tomograms (P < 0.001). Electron microscopy showed open endothelial tight junctions in 0/2 non-neoplastic human brain specimens and 2/2 high-grade astrocytomas. We suggest that loss of 55-kDa occludin expression in human brain tumours may contribute to endothelial tight junction opening. Characterizing the molecular pathology of brain endothelial tight junctions may facilitate the design of novel drugs against cerebral oedema.

Adenocarcinoma↗
PubMed2000

Occludin modulates transepithelial migration of neutrophils.

Neutrophils cross epithelial sheets to reach inflamed mucosal surfaces by migrating along the paracellular route. To avoid breakdown of the epithelial barrier, this process requires coordinated opening and closing of tight junctions, the most apical intercellular junctions in epithelia. To determine the function of epithelial tight junction proteins in this process, we analyzed neutrophil migration across monolayers formed by stably transfected epithelial cells expressing wild-type and mutant occludin, a membrane protein of tight junctions with four transmembrane domains and both termini in the cytosol. We found that expression of mutants with a modified N-terminal cytoplasmic domain up-regulated migration, whereas deletion of the C-terminal cytoplasmic domain did not have an effect. The N-terminal cytosolic domain was also found to be important for the linear arrangement of occludin within tight junctions but not for the permeability barrier. Moreover, expression of mutant occludin bearing a mutation in one of the two extracellular domains inhibited neutrophil migration. The effects of transfected occludin mutants on neutrophil migration did not correlate with their effects on selective paracellular permeability and transepithelial electrical resistance. Hence, specific domains and functional properties of occludin modulate transepithelial migration of neutrophils.

Actins↗
PubMed2000

Modulation of epithelial and endothelial paracellular permeability by leukocytes.

The tight junction acts as a regulated barrier for diffusion of ions, larger solutes, and migration of leukocytes through the paracellular space. Barrier function varies with the tissue type, and positively correlates with the number and complexity of tight junction strand formation. Polarized epithelia and brain capillary endothelium display a high degree of barrier function and tight junction formation. Conversely, vascular endothelium in other tissues has fewer, loosely organized tight junctions strands and greater permeability. Through cytoskeletal association, the tight junction and the adherens junction form a functional unit termed the apical junction complex. The development and stabilization of the tight junction is dependent upon the adherens junction. It has become apparent that paracellular permeability is altered during the migration of leukocytes across the apical junction complex and that the apical junction complex plays an important role in the regulation of leukocyte transmigration (or extravasation) through the endothelium and epithelium. Evidence suggests that important cell-cell adhesive events between transmigrating leukocytes and the apical junction complex and subsequent signaling events result in the facilitation of the passage of cells through the paracellular space. Possible mechanisms for the regulation of barrier function pertaining to leukocyte transmigration are discussed.

Animals↗
PubMed1975

Junctions in the meninges and marginal glia.

The meninges of various mammals were prepared for examination with the electronmicroscope by thin sectioning or freeze-fracturing. Particular attention was given to the distribution of tight junctions in order to determine the basis for the meningeal barrier between the blood circulating in dural vessels and the cerebrospinal fluid in the subarachnoid space. While some dural blood vessels are fenestrated, those in the subarachnoid space are not and their component endothelial cells are joined by an extensive system of tight junctions. An extensive and continuous system of tight junctions was also found in a layer of specialized cells at the border of the arachnoid with the dura. This arachnoid barrier layer is apparently the only basis of the meningeal barrier because often cellular layers in the dura and arachnoid lack tight junctions although they are linked by gap junctions and desmosomes. In particular, tight junctions are lacking at the border of the "subdural space" which is actually a fascial plane within the dura. Tight junctions are also lacking between astrocytes at the surface of the brain but these cells are linked by gap junctions and a new type of intercellular junction. The distribution of these junctions, as well as assemblies of intramembranous particles at the astrocytic border, raises the question whether this layer might have a role in the exchange of certain substances between the brain and cerebrospinal fluid.

Animals↗
PubMed2000

Chemical hypoxia-ischemia induces apoptosis in cerebromicrovascular endothelial cells.

Cerebral endothelial cell (CEC) death from ischemia may exacerbate brain injury by altering microvascular integrity, but little is known concerning the pattern of CEC death and disruption of tight junction between two CECs to ischemia. To address these questions, CECs were isolated from bovine, cultured, and placed in glucose-free medium containing sodium cyanide. Trypan blue staining shown that sodium cyanide resulted in a dose-dependent insult of CECs (10-80 mM). CEC injury increased progressively with the duration of 20 mM cyanide exposure, becoming significant (71%) after 12 h. The mode of cell death induced by cyanide is clearly apoptosis in CECs, as shown by Hoechst 33,342 staining and transmission electron microscope, i.e. cyanide induced condensation and margination of chromatin, nuclear fragmentation and shrinkage of cell body and condensed apoptotic bodies in CECs. Most importantly, we found that the tight junction between two CECs was disrupted 12 h after chemical-ischemia, i.e. when CECs underwent apoptosis, the tight junctional complexes became thinner and rough; the cleft of tight junction between two CECs became blurred and more wider, and membranes of tight junction were course and irregular; and the adherens junctions were damaged. These results indicate that chemical hypoxia-ischemia induces apoptotic cell death in CECs and alters the microvascular integrity by disrupting tight junction complexes, and suggest that CEC apoptotic death and disruption of tight junction may exacerbate ischemic insults to brain. Thus, prevention of CEC apoptotic death may contribute to improvements of ischemic insults.

Animals↗
PubMed1999

Cellular immunolocalization of occludin during embryonic and postnatal development of the mouse testis and epididymis.

Cellular junctions in the testis and epididymis play crucial roles for the development and maturation of spermatozoa. In the testis, tight junctions between Sertoli cells form a functional blood testis barrier between 10 and 16 days of age, whereas the tight junctional blood epididymal barrier between adjacent epithelial cells is formed between days 18 and 21. In the present study, occludin, a constituent integral membrane protein of tight junctions, was localized by immunofluorescent confocal microscopy in embryonic (days 13.5-18.5), postnatal (days 5-23) and adult (day 70) mouse testes and epididymides to correlate its expression with the onset of tight junctions and eventual formation of these barriers. At embryonic days 13.5 and 16.5, low diffuse cytoplasmic levels of occludin were observed in cells of the testicular cords. By embryonic day 18.5, the level of occludin was still low but appeared as a filiform-like network streaming toward the center of the cord. At postnatal days 5 and 7 immunostaining became more intense and appeared to outline the periphery of Sertoli cells of seminiferous tubules. Postnatal day 14 marked the appearance of an intense, focal band-like localization of occludin at the base of the tubules, correlating with the appearance of a functional blood-testis barrier. By day 23 and in adults, expression of occludin was noted at the base of the tubule appearing as intense, wavy, discontinuous bands similar in appearance irrespective of the stage of the seminiferous epithelium cycle. In the developing epididymis, intense cytoplasmic immunostaining was present in epithelial cells of many epididymal tubules at embryonic day 13.5. By embryonic day 16.5, intense occludin immunostaining appeared along the lateral plasma membranes of epithelial cells, whereas at embryonic day 18.5, immunostaining was punctate and apically located, suggesting the presence of tight junctions by this age; similar immunostaining was noted at postnatal days 5 and 7. In the adult epididymis, distinct punctate apical staining was observed between adjacent principal cells of all epididymal regions except the proximal initial segment, where occludin was found only in association with narrow cells. These results indicate that in the epididymis, the appearance of occludin at apical sites between adjacent epithelial cells occurs during embryonic development suggesting that tight junctions form earlier than in the testis. While occludin was expressed in a similar pattern between Sertoli cells at all stages of the cycle in the adult testis, its expression in the adult epididymis was cell- and region-specific. Taken together these data suggest that different factors regulate occludin expression in the testis and epididymis.

Aging↗
PubMed2002

Tightening of endothelial cell contacts: a physiologic response to cocultures with smooth-muscle-like 10T1/2 cells.

Tightening of endothelial cell-to-cell contacts is an important event at the end of angiogenesis in order to achieve controlled transfer of solutes between the blood stream and solid tissues. We found that tightening of endothelial cell-to-cell contacts and the formation of a permeability barrier can be induced in vitro by dibutyryl cAMP and hydrocortisone. This process is accompanied by increased junctional localization and cytoskeletal association of the adherens junctional plakoglobin and the tight junction associated proteins ZO-1, ZO-2, and occludin. Based on these findings, we proceeded to investigate whether smooth-muscle-like mesenchymal cells would influence endothelial junctional differentiation. For this purpose, human umbilical chord vein endothelial cells and murine smooth-muscle-like 10T1/2 cells were cocultivated and compared with their respective monocultures. Immunofluorescence on cells and Western blot analyses were performed for marker proteins of adherens and tight junctions. Functional permeability assays were performed for the tracer molecule biotin-dextran. The results indicated that 10T1/2 cells induced the tightening of endothelial cell-to-cell contacts. Plakoglobin, ZO-1, ZO-2, and occludin showed increased junctional localization when 10T1/2 cells were present. Cocultures also displayed a significantly higher permeability barrier for the tracer molecule biotin-dextran. In conclusion, mural cells such as smooth muscle cells and pericytes may be important for stabilizing endothelial cell-to-cell contacts and may influence vessel-type specific differences of the endothelial phenotype.

Adherens Junctions↗
PubMed1979

Control of mucus secretion and ion transport in airways.

The output of secretions from the airway submucosal glands is regulated by vagal efferent nerves. Stimulation of cough receptors increases mucus output reflexly via the vagus nerves. Adrenergic agonists increase submucosal gland secretions in some species, which indicates that adrenergic receptors are present in these cells. However, evidence for adrenergic nervous pathways to the glands is limited. Irritants and drugs stimulate secretion from epithelial cells by direct effects. There is also evidence that the secretion of epithelial cells can be stimulated by parasympathetic nervous pathways in birds but not in mammals. Active ion transport of Cl- toward the lumen and of Na+ toward the submucosa results in net ion movement toward the airway lumen in unstimulated tracheal epithelia. Drugs and mediators increase the net movement of ions toward the lumen. No agents have yet been found that increase net ion movement toward the submucosa. The link between ion transport and water secretion in airway epithelia, although speculative, seems likely in view of the evidence from other epithelia. Since airway epithelium is a "tight junction" epithelium, modification of the tight junction may alter the transepithelial movement of water and ions. We suggest that the depth and consistency of the periciliary layer of airway secretions determine the ability of the cilia to propel the mucoprotein gel and thereby modify mucociliary transport. To achieve this, secretion of mucus must be controlled separately from the secretion of water. Studies are needed to determine which of the specialized functions of the epithelial cells interact to regulate the clearance of secretions from the airway. Is the sol maintained by secretion and reabsorption of fluid across the epithelium? Does the sol move with the gel by ciliary action or does it remain stationary? Do changes in the epithelial tight junctions influence net water movement and thus indirectly alter the depth of the sol layer? To answer these questions, techniques are needed to study subunits of the airway, including isolated surface cells and submucosal glands; and sensitive methods are required to analyze the very small samples of secretions for glycoprotein and electrolyte content. Intracellular measurements of electrolyte concentrations and electrical potentials may help to elucidate the mechanisms of transepithelial ion and water movement. The control system for the production and removal of respiratory tract secretions may be altered in disease. For instance, chronic stimulation of cough receptors causes reflex secretion and may be the cause of the hyperplasia of submucosal glands and of the abnormal secretions that occur in chronic bronchitis and asthma (50, 58). The abnormally viscid mucus in cystic fibrosis may be due to a defect in Cl- transport, which provides too little water for both the gel and sol layers. These speculations are intended to identify areas for further research, which hopefully will reduce the morbidity and mortality in these common lung diseases.

Animals↗
PubMed1997

Bacterial lipopolysaccharide reduced intestinal barrier function and altered localization of 7H6 antigen in IEC-6 rat intestinal crypt cells.

The intestinal epithelial barrier restricts the passage of potentially toxic substances into the systemic circulation and is considered to be mostly mediated by tight junctions, though the mechanisms involved in the regulation of intestinal tight junctions are not yet fully understood. In the present study, we examined whether bacterial lipopolysaccharide (LPS) altered the barrier function of tight junction and localization of tight junctional proteins, ZO-1 and 7H6 antigen, in IEC-6 intestinal cells. Administration of LPS to the basolateral surface of IEC-6 cells disrupted the barrier function and caused the disappearance of 7H6 antigen from the cell border, whereas LPS administered to the apical surface altered neither the barrier function nor the localization of 7H6 antigen in IEC-6 cells. On the other hand, the localization of ZO-1 was not influenced by these treatments of LPS. These results suggest that the interaction of LPS with the basolateral surface of intestinal epithelial cells disrupts the barrier function and 7H6 antigen take part in the maintenance of the barrier function in IEC-6 cells.

Animals↗