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At least 109 records · Page 6Linked to original sources
PubMed1987

Polyomavirus middle T antigen downregulates junctional cell-to-cell communication.

We examined the effect of polyomavirus middle T antigen on cell-to-cell communication in rat F cells transfected with an inducible middle T recombinant DNA or infected with a conditional mutant virus. Junctional permeability fell (reversibly) when middle T transcription was induced or when middle T was switched to the transformation+ form. The effect correlates with the rise of protein tyrosine kinase activity.

Animals↗
PubMed2003

Discrete models of autocrine cell communication in epithelial layers.

Pattern formation in epithelial layers heavily relies on cell communication by secreted ligands. Whereas the experimentally observed signaling patterns can be visualized at single-cell resolution, a biophysical framework for their interpretation is currently lacking. To this end, we develop a family of discrete models of cell communication in epithelial layers. The models are based on the introduction of cell-to-cell coupling coefficients that characterize the spatial range of intercellular signaling by diffusing ligands. We derive the coupling coefficients as functions of geometric, cellular, and molecular parameters of the ligand transport problem. Using these coupling coefficients, we analyze a nonlinear model of positive feedback between ligand release and binding. In particular, we study criteria of existence of the patterns consisting of clusters of a few signaling cells, as well as the onset of signal propagation. We use our model to interpret recent experimental studies of the EGFR/Rhomboid/Spitz module in Drosophila development.

Animals↗
PubMed2005

Direct cell-cell communication: a new approach derived from recent data on the nature and self-organisation of ultradian (circahoralian) intracellular rhythms.

Recent data concerning ultradian (circahoralian) intracellular rhythms are used to assess the biochemical mechanisms of direct cell-cell communication. New results and theoretical considerations suggest a fractal nature of ultradian rhythms and their self-organisation. The fundamental and innate nature of these rhythms relates to their self-similarity at different levels of cell and tissue organisation. They can be detected in cell-free systems as well as in cells and organs in vivo. Such rhythms are a means of finding an optimal state of cell function rather than achieving a state of absolute stability. As a consequence, oscillations, being irregular and numerous by the set of periods, are resilient to functional overload and injury. Recent data on the maintenance of their fractal structure and, especially on the selection of optimal periods are discussed. The positive role of chaotic dynamics is stressed. The ultradian rhythm of protein synthesis in hepatocytes in vitro was used as a marker of direct cell-cell communication. The system demonstrates cell cooperation and synchronisation throughout the cell population, and suggests that the ultradian rhythms are self-organised. These observations also led to the detection of mechanisms of direct cell-cell communication in which extracellular factors have an essential role. Experimental evidence indicated the involvement of gangliosides and/or catecholamines in this large-scale synchronisation of protein synthesis. The response of all, or a major part, of the cell population is important; after the initial trigger effect, a periodic pattern is retained for some time. The influence of Ca2+-dependent protein kinases on protein phosphorylation can be a final step in the phase modulation of rhythms during cell-cell synchronisation. The intercellular medium plays an important role in self-synchronisation of ultradian rhythms between individual cells. Low cooperative activity of hepatocytes of old rats resulted from altered composition of the intercellular medium rather than direct effects of animal and cellular ageing. Similarly, in the whole body, changes in levels of gangliosides and catecholamines in the blood serum, a natural intercellular medium, can be critical events in age-dependent changes of the serum and accordingly cell-cell synchronisation. Hepatocytes of old rats exhibit some of the properties of young cells following an increase in blood serum ganglioside level, as well as, in in vitro conditions, after the addition of gangliosides to the culture medium. Together with data on ultradian functional and metabolic rhythms, all the material reviewed here allows us to propose a mechanism of direct cell-cell cooperation via the medium in which the cells exist, that supplements the nervous and hormonal central regulation of organ functions. Ultradian intracellular rhythms may thus provide a finer framework within which the integrated dynamics of respiration, heart rate, brain activity, and even behavioural patterns, are brought to an optimal functional pattern. Innate and direct cell-cell cooperation may have been employed as a means of intercellular regulation during the course of metazoan evolution, that preceded nervous regulation and is presently retained in mammals.

Activity Cycles↗
PubMed2004

A bacterial cell-cell communication signal with cross-kingdom structural analogues.

Extracellular signals are the key components of microbial cell-cell communication systems. This report identified a diffusible signal factor (DSF), which regulates virulence in Xanthomonas campestris pv. campestris, as cis-11-methyl-2-dodecenoic acid, an alpha,beta unsaturated fatty acid. Analysis of DSF derivatives established the double bond at the alpha,beta positions as the most important structural feature for DSF biological activity. A range of bacterial pathogens, including several Mycobacterium species, also displayed DSF-like activity. Furthermore, DSF is structurally and functionally related to farnesoic acid (FA), which regulates morphological transition and virulence by Candida albicans, a fungal pathogen. Similar to FA, which is also an alpha,beta unsaturated fatty acid, DSF inhibits the dimorphic transition of C. albicans at a physiologically relevant concentration. We conclude that alpha,beta unsaturated fatty acids represent a new class of extracellular signals for bacterial and fungal cell-cell communications. As prokaryote-eukaryote interactions are ubiquitous, such cross-kingdom conservation in cell-cell communication systems might have significant ecological and economic importance.

Bacterial Proteins↗
PubMed1988

Concentration/response effect of 2,2', 4,4', 5,5'-hexabromobiphenyl on cell-cell communication in vitro: assessment by fluorescence redistribution after photobleaching ("FRAP").

Inhibition of gap junction-mediated cell-cell communication might be a mechanism for several types of cellular dysfunctions, including tumor promotion. Although many different assays have been designed to measure gap junction-mediated intercellular communication, we applied a new technique, termed Fluorescence Redistribution After Photobleaching ("FRAP"), to assess the ability of a known tumor promoter, 2,2', 4,4', 5,5'-hexabromobiphenyl (245-HBB), to inhibit cell-cell communication in a concentration-dependent manner. WB-F344 (rat epithelial) cells were plated at low density, exposed to noncytotoxic concentrations of 1, 5, or 20 micrograms 245-HBB/ml medium, and stained with 6-carboxyfluorescein diacetate. Single cells in pairs or clusters of touching cells in each exposure group were examined with FRAP. The results revealed an inverse correlation between the degree of fluorescence redistribution in photobleached cells and the concentration of 245-HBB. Therefore, FRAP appears to be a sensitive and rapid technique for determining complete or partial inhibition of chemically induced intercellular communication in vitro. These results also provide further evidence for the ability of 245-HBB to inhibit gap junction-mediated cell-cell communication in a concentration-dependent manner.

Cell Communication↗
PubMed2006

Dietary modulation of the multistage, multimechanisms of human carcinogenesis: effects on initiated stem cells and cell-cell communication.

Diet can influence the risk to cancer in both negative and positive ways. Worldwide, more than 10 million persons develop cancer annually. Diet could prevent many cancers. Carcinogenesis is a multistage, multimechanism process, consisting of "initiation," "promotion," and "progression" phases. Although diet could affect each phase, an efficacious strategy for dietary chemoprevention would be intervention during the promotion phase. The tumor-promotion process requires sustained exposure to agents that stimulate the growth and inhibition of apoptosis of initiated cells in the absence of antipromoters. Chronic inflammation has been associated with the promotion process. The mechanism affecting the promotion process appears to be the inhibition of cell-cell communication between normal and initiated cells. Most, if not all, tumor-promoting agents and conditions, reversibly, inhibit cell-cell communication, whereas antipromoters, antioxidants, and anti-inflammatory agents have been shown to ameliorate the effects of tumor promoters on cell-cell communication. Additionally, adult stem cells are hypothesized to be the target cells for initiating the carcinogenic process. A new paradigm has been presented that postulates the first function of the carcinogenic process is to block the "mortalization" of a normal, "immortal" adult stem cell rather than the induction of "immortalization" of a normal mortal cell.

Anticarcinogenic Agents↗
PubMed1994

Cell-to-cell communication in a differentiating ovine lens culture system.

PURPOSE: This study was performed to determine whether the junctions between both the epithelial and the differentiating fiber-like cells of ovine lens cultures, like gap junctions in other tissues, exhibit cell-to-cell communication that is inhibited by n-octanol, and to determine whether lens connexins and the fiber cell membrane proteins MP20 and MP26 are expressed by these ovine lens cell cultures. METHODS: Cells were injected with Lucifer yellow CH to measure cell-to-cell communication. Antibodies to connexin-related lens membrane protein MP70, connexin 43 (Cx43), and connexin 46 (Cx46) and to membrane proteins MP20 and MP26 were used to immunofluorescently label lens cultures and probe Western blots of membranes isolated from lens cultures. RESULTS: Both epithelial cells and differentiating clear cells exhibited cell-to-cell transfer of Lucifer yellow that was inhibited by n-octanol. Although a Cx43 antibody immunofluorescently labeled small plaques between the epithelial cells, an MP70 antibody labeled large plaques as well as small punctate areas of the differentiating fiber-like cells. It is interesting that Cx43 and MP70 were frequently present in the same plaques at cell interfaces between epithelial cells as well as some of the larger plaques on the differentiating fiber-like cells. Cx46 and MP70 antibodies labeled the same plaques in membranes of differentiating fiber-like cells and late-stage epithelial cells. The electrophoretic mobility of all three connexin proteins was modified after treatment with alkaline phosphatase. Immunohistochemical staining of these differentiating regions and Western immunoblotting of purified membranes derived from differentiated cultures also showed the presence of MP20 and MP26. CONCLUSIONS: The different cell types in the ovine lens culture exhibit gap junction-mediated cell-to-cell communication that is likely effected by one or more of the connexin proteins.

1-Octanol↗
PubMed2004

Role of cell-cell communication in inhibiting butyric acid-induced T-cell apoptosis.

We have previously demonstrated that human gingival fibroblasts rescue butyric acid-induced T-cell apoptosis via proinflammatory cytokines such as interleukin 6 (IL-6) and IL-11, which are produced by fibroblasts stimulated with butyric acid. In this study, we determined if T-cell adhesion to human gingival fibroblasts influenced the susceptibility of T cells to butyric acid-induced apoptosis. We have shown that the number of Jurkat T cells adherent to gingival fibroblasts (Gin-1 cells) was significantly increased by the addition of butyric acid. All Jurkat cells that adhered to Gin-1 cells remained viable, while the nonadherent Jurkat cells dropped into apoptosis. The increase in T-cell adhesion to fibroblasts was also observed when Jurkat cells, but not Gin-1 cells, were pretreated with butyric acid. The expression levels of CD44, very late antigen 2 (VLA-2) and VLA-5 but not of leukocyte function-associated antigen 1 (LFA-1) and VLA-4 on Jurkat cells were increased following treatment with butyric acid. Furthermore, pretreatment of butyric acid-sensitized Jurkat cells with monoclonal antibodies against CD44, VLA-2, and VLA-5, but not LFA-1 and VLA-4, followed by coculture with Gin-1 cells inhibited T-cell adhesion to fibroblasts and increased apoptosis of nonadherent T cells after coculture of gingival fibroblasts and Jurkat cells. These results indicate that T-cell adherence to fibroblasts is enhanced by butyric acid and that butyric acid-induced T-cell apoptosis is down-regulated by T-cell adhesion to gingival fibroblasts through an interaction with the adhesion molecules CD44, VLA-2, and VLA-5 expressed on T cells stimulated with butyric acid.

Antibodies, Monoclonal↗
PubMed1991

Rat ovarian granulosa cell culture: a model system for the study of cell-cell communication during multistep transformation.

A spontaneously immortalized clonal granulosa cell line (SIGC) derived from primary rat ovarian granulosa cell cultures was developed as a model system to explore the process of transformation using an epithelial cell type. SIGC has an epithelial morphology and grows in culture without undergoing luteinization. The cell line is thought to represent an intermediate step in carcinogenesis because it seems to grow indefinitely in culture but does not form clones in soft agar or tumors in nude mice. Indirect immunofluorescence and Western blot analysis verified the constitutive expression of the recessive oncogene product p53 in the cell line, thereby suggesting a possible mechanism of immortalization. Ultrastructural studies indicated that SIGC cells are characterized by an undifferentiated phenotype with prominent intermediate filaments, desmosomes, and gap junctions. The identification of cytokeratin by indirect immunofluorescence and Western blot analysis suggests that SIGC functions as an epithelial cell type. Functional studies of cell-cell communication by a dye transfer technique (fluorescence recovery after photobleaching) showed reduced communication compared to normal primary granulosa cells in culture. SIGC cells were transfected with early region genes of SV40 virus in an attempt to generate fully transformed cell lines. The resulting cell line SV-SIGC expressed T-antigen, was anchorage independent, formed tumors in nude mice, and had reduced intercellular communication as compared to SIGC cells. Explants from the tumors in nude mice were used to generate another cell line (T-SV-SIGC), which exhibited further reduction in both the incidence and the rate of communication. These results clearly demonstrated a progressive loss of functional communication during multistep transformation of an ovarian cell type. These data demonstrate that this assay system based on an epithelioid cell type can be used to study the relationship between intercellular communication and the multistep process of carcinogenesis.

Animals↗
PubMed2006

Impaired cell communication in the diabetic heart. The role of the renin angiotensin system.

The influence of diabetes mellitus on the process of cell communication and impulse propagation was investigated in trabeculae isolated from the ventricle of diabetic rat hearts. Diabetes was produced by a single intraperitoneal injection of streptozotocin (60 mg/Kg). Cell-to-cell spread of Lucifer yellow CH was studied with the cut-end method. Measurements of the diffusion coefficient of Lucifer Yellow CH (D) was made by fitting the experimental results to theoretical points using an interactive computer program for non-linear regression. The results indicated an average value of D of 3 +/- 0.8x10(-7 )cm(2)/s for the controls (n = 5) and 3.8 +/- 0.5x10(-8 )cm(2)/s (n = 7) (p < 0.05) for diabetic hearts. No change of efflux of the dye through the surface cell membrane was found in diabetic rat compared to controls (p > 0.05). Moreover, the dye binding in the cytosol of diabetic heart was not significantly different from controls. The calculated values of junctional permeability for the dye was found to be p (j) = 1.5x10(-3 )cm/s for control and 1.5x10(-5 )cm/s for diabetic heart. To investigate the possible role of the activation of the renin-angiotensin system (RAS) on the change in cell communication, diabetic rats were treated with enalapril (25 mg/Kg/day) for a period of 14 days. Measurements of the diffusion coefficient (D) of the dye indicated a significant increase of D (6.7 +/- 1.1x10(-7 )cm(2)/s) (n = 4) (p < 0.05) compared with diabetic rats not exposed to enalapril. No change on efflux of the dye or cytoplasmic binding was found in animals treated with enalapril. The calculated value of junctional permeability showed a significant increase (p (j) = 3.9x10(-4 )cm/s) in presence of enalapril compared with controls. In addition, angiotensin II (10(-8 )M) added to the bath caused a significant decrease of conduction velocity in cardiac muscle of diabetic heart. In conclusion, Cell communication and impulse propagation are significantly impaired in the ventricle from diabetic rats, a phenomenon partly related to the activation of the RAS.

Animals↗
PubMed1988

Wound healing, cell communication, and DNA synthesis during imaginal disc regeneration in Drosophila.

Wound healing, gap-junctional cell communication, and DNA synthesis were studied in 3/4 fragments of the imaginal wing disc of Drosophila melanogaster cultured in the female adult abdomen. Such fragments regenerate the missing sector by cell proliferation over a period of several days. Individual cells were marked in the starting fragment by intracellular injection of high-molecular-weight lysinated rhodamine dextran, and the positions of the marked cells were determined by fluorescence microscopy before and after various culture times. These experiments showed that cells along the two wound edges were brought together by wound healing during the first day of the culture period. The marked cells then gradually moved apart over the next 3 days as new cells were added between them by intercalary regeneration. Gap-junctional cell communication across the healed wound, assessed by the movement of intracellularly injected small fluorescent dye molecules, was not detectable after 1 day of culture. After 2 days there was some dye transfer into the growth zone but not as much as in other directions. After 3 days there was significant dye transfer into the growth zone. DNA synthesis, detected by immunolocalization of incorporated bromodeoxyuridine, was first apparent at 18 hr after the beginning of the culture period; at this time as well as at later times it occurred only in the immediate vicinity of the healed wound. DNA synthesis was stimulated over a distance of several cell diameters from the wound, and for one of the cuts it was much more prevalent on one side of the wound than on the other. The results indicate that wound healing brings together cells from distant positions in the disc, and that the response to this is local DNA synthesis and cell proliferation. Gap-junctional communication across the wound does not appear to be necessary for stimulating this cell proliferation, although the timing of the reappearance of gap-junctional communication suggests that it may be involved in terminating proliferation.

Animals↗
PubMed2005

Renal cell-to-cell communication via extracellular ATP.

In the kidney, macula densa cells communicate with the mesangial cell-afferent arteriolar smooth muscle cell complex through ATP signaling. This signaling process involves release of ATP across the macula densa basolateral membrane through a maxi anion channel and the interaction of ATP with purinergic P2 receptors.

Adenosine Triphosphate↗
PubMed1995

Gap junction-mediated cell-to-cell communication in bovine and human adrenal cells. A process whereby cells increase their responsiveness to physiological corticotropin concentrations.

We have studied the role of gap junction-mediated intercellular communication on the steroidogenic response of bovine (BAC) and human (HAC) adrenal fasciculo-reticularis cells in culture to corticotropin (ACTH). Indirect immunofluorescence analyses showed that intact human and bovine adreno-cortical tissue as well as HAC and BAC in culture expressed the gap junction protein connexin43 (also termed alpha 1 connexin). Both HAC and BAC were functionally coupled through gap junctions as demonstrated by microinjection of a low molecular mass fluorescent probe, Lucifer yellow. The cell-to-cell transfer of the probe was blocked by 18 alpha-glycyrrhetinic acid (GA), an inhibitor of gap junction-mediated intercellular communication. GA markedly decreased the steroidogenic response (cortisol production) of both HAC and BAC to low (10 pM) but not to high (5 nM) concentrations of ACTH. GA had no inhibitory effect on the steroidogenic response to 8 Br-cAMP (at either low or high concentrations) and did neither modify the binding of 125I-ACTH to its receptor nor the ACTH-induced cAMP production. BAC cultured at high or low cell densities (2.4 x 10(5) vs. 0.24 x 10(5) cells/cm2) exhibited distinct levels of intercellular communication and were differently responsive to sub-maximal ACTH concentrations. The ACTH ED50 values for cortisol production were 8.5 +/- 1.3 and 45 +/- 14 pM (P < 0.02) for BAC cultured at high and low density, respectively. In the presence of GA, there was a shift of the ACTH concentration-response curves in the two culture conditions. The ACTH ED50 of high density and low density cultured BAC increased 25- and 5-fold, respectively, and became similar (220 +/- 90 and 250 +/- 120 pM). These results demonstrate that gap junction-mediated communication between hormone-responsive and nonresponsive cells is one mechanism by which adrenal cells increase their responsiveness to low ACTH concentrations.

Adrenal Cortex↗
PubMed2004

Programmed population control by cell-cell communication and regulated killing.

De novo engineering of gene circuits inside cells is extremely difficult, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells. Here we demonstrate that by coupling gene expression to cell survival and death using cell-cell communication, we can programme the dynamics of a population despite variability in the behaviour of individual cells. Specifically, we have built and characterized a 'population control' circuit that autonomously regulates the density of an Escherichia coli population. The cell density is broadcasted and detected by elements from a bacterial quorum-sensing system, which in turn regulate the death rate. As predicted by a simple mathematical model, the circuit can set a stable steady state in terms of cell density and gene expression that is easily tunable by varying the stability of the cell-cell communication signal. This circuit incorporates a mechanism for programmed death in response to changes in the environment, and allows us to probe the design principles of its more complex natural counterparts.

Cell Division↗