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At least 721 records · Page 40Linked to original sources
PubMed1995

Insulin-like growth factor-I promotes cell proliferation in the absence of modulation of collagen phenotypes and utilizes IRS-1, not PLC-gamma 1, in corneal endothelial cells.

Corneal endothelial cells are differentiated cells and are thus incapable of physiologic regeneration. In a search for a growth factor that would promote optimal proliferation of corneal endothelial cells in the absence of other modulating activities, the effect of insulin-like growth factor-I (IGF-I) on rabbit corneal endothelial cells was studied. In addition, cellular effector molecules responsible for the signal pathway for IGF-I were studied. IGF-I at 50 ng/ml stimulated corneal endothelial cell proliferation after at least 8 h of treatment. IGF-I did not change cell shape of corneal endothelial cells: the cells treated with IGF-I at 50 ng/ml maintained polygonal morphology regardless of the duration of exposure. IGF-I did not alter collagen phenotypes either qualitatively or quantitatively: the treated cells continued to synthesize types IV and VIII collagen, as did the control cells. The steady-state levels of alpha 2(I) collagen RNA and alpha 2(IV) RNA were not altered by IGF-I treatment. Immunohistochemical analysis showed that IGF-I is present in corneal endothelium in vivo, while the underlying Descemet's membrane demonstrated no staining. Corneal endothelial cells also produce IGF binding protein-2 (IGFBP-2), which appears to bind IGF-I that has been introduced exogenously in the medium. Further investigation as to how the signals of IGF-I were transmitted for the biological activities demonstrated that the expression of insulin receptor substrate-1 (IRS-1) is up-regulated by IGF-I treatment, while PLC-gamma 1 expression is not altered by this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

pp60(c-src) modulates microvascular endothelial phenotype and in vitro angiogenesis.

The tyrosine kinase c-src associates with the platelet-derived growth factor (PDGF) receptor. Overexpression of wild-type c-src, a kinase-negative c-src mutant, and v-src in microvascular endothelial cells modulated the mitogenic effect of PDGF, suggesting that c-src kinase activity inhibits PDGF signals. Analyses of cell morphology in two-dimensional culture revealed changes in cell shape and size induced by the overexpression of c-src proteins. Investigations in three-dimensional culture unveiled a modulatory role of c-src during in vitro angiogenesis. Overexpression of c-src resulted in an increased diameter of tube-like structures, and the number of branching segments was decreased. Expression of the kinase-negative c-src mutant resulted in abortive tube formation consisting of disconnected multicellular fragments. These results indicate that the c-src tyrosine kinase exerts regulatory effects on endothelial proliferation, size, and cytoskeletal organization in two-dimensional culture and on the formation of a differentiated multicellular network in three-dimensional culture.

Adipose Tissue↗
PubMed1992

Glucocorticoids promote development of the osteoblast phenotype by selectively modulating expression of cell growth and differentiation associated genes.

To understand the mechanisms by which glucocorticoids promote differentiation of fetal rat calvaria derived osteoblasts to produce bone-like mineralized nodules in vitro, a panel of osteoblast growth and differentiation related genes that characterize development of the osteoblast phenotype has been quantitated in glucocorticoid-treated cultures. We compared the mRNA levels of osteoblast expressed genes in control cultures of subcultivated cells where nodule formation is diminished, to cells continuously (35 days) exposed to 10(-7) M dexamethasone, a synthetic glucocorticoid, which promotes nodule formation to levels usually the extent observed in primary cultures. Tritiated thymidine labelling revealed a selective inhibition of internodule cell proliferation and promotion of proliferation and differentiation of cells forming bone nodules. Fibronectin, osteopontin, and c-fos expression were increased in the nodule forming period. Alkaline phosphatase and type I collagen expression were initially inhibited in proliferating cells, then increased after nodule formation to support further growth and mineralization of the nodule. Expression of osteocalcin was 1,000-fold elevated in glucocorticoid-differentiated cultures in relation to nodule formation. Collagenase gene expression was also greater than controls (fivefold) with the highest levels observed in mature cultures (day 35). At this time, a rise in collagen and TGF beta was also observed suggesting turnover of the matrix. Short term (48 h) effects of glucocorticoid on histone H4 (reflecting cell proliferation), alkaline phosphatase, osteopontin, and osteocalcin mRNA levels reveal both up or down regulation as a function of the developmental stage of the osteoblast phenotype. A comparison of transcriptional levels of these genes by nuclear run-on assays to mRNA levels indicates that glucocorticoids exert both transcriptional and post-transcriptional effects. Further, the presence of glucocorticoids enhances the vitamin D3 effect on gene expression. Those genes which are upregulated by 1,25(OH)2D3 are transcribed at an increased rate by dexamethasone, while those genes which are inhibited by vitamin D3 remain inhibited in the presence of dexamethasone and D3. We propose that the glucocorticoids promote changes in gene expression involved in cell-cell and cell-extracellular matrix signaling mechanisms that support the growth and differentiation of cells capable of osteoblast phenotype development and bone tissue-like organization, while inhibiting the growth of cells that cannot progress to the mature osteoblast phenotype in fetal rat calvarial cultures.

Alkaline Phosphatase↗
PubMed2004

Modulation of antigenic phenotype by IL-1beta, IFNgamma and TGFbeta on cultured human decidual stromal cells.

Decidual stromal cells (DSC) constitute the most abundant population in normal human decidua together with leukocytes. Both populations may be involved in the immunological role of the decidua by favoring gestational functions, participating in physiological mechanisms to eliminate the fetus, or providing local defense against infection. Using flow cytometry, we investigated whether different cytokines modulate the expression on cultured DSC of antigen-presenting molecules. The treatment with IFNgamma or IL-1beta enhanced the expression of CD54. The percentage of expression of HLA-DR was enhanced by IL-1beta treatment but was not modified by IFNgamma. The expression of CD80 and CD86 was enhanced by IFNgamma treatment but was not modified by IL-1beta; the expression of CD86 and HLA-DR was reduced by TGFbeta1 treatment. The response of DSC and dendritic cells to these cytokines appears to be similar, suggesting a phenotypic and functional relationship between these cell types.

Antigen Presentation↗
PubMed2006

Modulation of chondrocyte phenotype for tissue engineering by designing the biologic-polymer carrier interface.

Therapeutic strategies based on cell and tissue engineering can be advanced by developing material substrates that effectively interrogate the biological compartment, with or without the complimentary local release of growth factors. Poly(ether ester) segmented copolymers were engineered as model material systems to elucidate the interfacial molecular events that govern the function of adhered cells. Surface chemistry was modulated by varying poly(ethylene glycol) (PEG) length and mole fraction with poly(butylene terephthalate) (PBT), leading to differential competitive protein adsorption of fibronectin and vitronectin from serum and consequently to different cell attachment modes. Adhesion within the hydrogel-like milieu of longer surface PEG was mediated via binding to the CD44 transmembrane receptor, rather than the RGD-integrin mechanism, whereas greater substrate-bound fibronectin resulted in cell adhesion via integrins. These adhesion modalities differentially impacted morphological cell phenotype (spread or spheroid) and the subsequent expression of mRNA transcripts (collagen types II, I) characteristic of phenotypically differentiated or dedifferentiated chondrocytes, respectively. These results demonstrate that materials can be designed to directly elicit the membrane bound receptor apparatus desired for downstream cellular response, without requiring exogenous biological growth factors to enable differentiated potential.

Blotting, Western↗
PubMed1998

Antiproliferative polysaccharides modulate distribution and phenotypic expression of collagens by gingival fibroblasts.

Gingival fibroblasts are particularly involved in the physiologic maintenance and repair of periodontium. During these processes, cell proliferation and synthesis of a collagen-rich gingival matrix should be controlled. A dextran derivative, namely, carboxy methyl dextran benzylamide sulfonate (CMDBS), considered to be a functional analog of heparin, was previously described to regulate proliferation of different types of cells and independently to modulate the expression of collagen biosynthesis. In this report, we demonstrate that CMDBS and heparin inhibited gingival fibroblast proliferation. We then analyzed collagen biosynthesis by measuring the incorporation of the radiolabeled [3H]proline precursor into collagen by postconfluent gingival fibroblasts. Our results showed CMDBS did not alter total collagen synthesis; it induced the preferential accumulation of newly synthesized collagen into the pericellular matrix; and it decreased the expression of type III collagen, particularly in the cell layer. Taken together, our results suggest that by inhibiting cell proliferation, CMDBS could induce the synthesis of an extracellular collagenous matrix which forms a network between gingival fibroblasts.

Adolescent↗
PubMed1984

Phenotypic variation and modulation in Bordetella bronchiseptica.

Most of the isolates of Bordetella bronchiseptica obtained by this laboratory possessed a characteristic colonial morphology when grown on Bordet- Gengou agar (BGA) at 37 degrees C. The colonies appeared domed (Dom+) with a smooth colonial surface (Scs+) and a clear zone of hemolysis ( Hly +). From these Dom+ Scs+ Hly + BGA colony types arose flat (Dom-), smooth colonial surface (Scs+) and nonhemolytic ( Hly -) variants at frequencies of 10(-2) to 10(-3). Isogenic pairs of Dom+ Scs+ Hly + and Dom- Scs+ Hly - BGA phenotype variants (BGA-PVs) were picked from 11 strains of B. bronchiseptica, and their whole cell lysates were compared with each other by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Characteristic SDS-PAGE profiles were observed for each of the Dom+ Scs+ Hly + and Dom- Scs+ Hly - BGA-PVs with regard to (i) surface-exposed proteins, based on autoradiographs of 125I- Iodogen -labeled organisms, (ii) polypeptide differences, based on gels stained with Coomassie brilliant blue R-250, and (iii) lipopolysaccharide differences based on gels stained with silver after oxidation with periodic acid. SDS-PAGE profiles were then used to monitor the phenotypes expressed by Dom+ Scs+ Hly + and Dom- Scs+ Hly - BGA-PVs transferred and grown on brucella agar, Trypticase soy agar, and nutrient agar. When grown on non-BGA media, the Dom+ Scs+ Hly + BGA-PVs from six of eight strains showed SDS-PAGE profiles identical to those of Dom- Scs+ Hly - BGA-PVs. This phenotypic change was reversible even after 15 subcultures on the non-BGA media, since Dom+ Scs+ Hly + organisms passed back onto BGA expressed both Dom+ Scs+ Hly + colonial morphology and Dom+ Scs+ Hly + SDS-PAGE profiles. The influence of cultural conditions on maintenance of virulence is discussed.

Animals↗
PubMed1988

Modulation of the phenotypic expression of a human serine tRNA gene by 5'-flanking sequences.

Mammalian nonsense suppressors provide a model system to investigate structural and functional aspects of mammalian tRNAs and their genes in vivo. To assess the role that extragenic flanking sequences may have on the expression of mammalian tRNA genes in vivo, deletion/substitutions ending in the 5'-flanking sequence or 3'-flanking sequence of a cloned human serine amber suppressor tRNA gene were constructed. The phenotypic expression of these mutant genes was examined by transfection in mammalian cells and by measuring the efficiency with which they were able to suppress an amber (UAG) nonsense mutation in the Escherichia coli chloramphenicol acetyl transferase (cat) gene. Deletion of the 5'-flanking region up to nucleotide position -66 with respect to the first nucleotide of the coding region had no effect on levels of nonsense suppression as compared to the wild-type gene; however, deletion to -18 led to a 12-fold reduction in suppressor activity. Deletion up to -1 did not further reduce suppression efficiency. Deletion of the 3'-flanking region up to 9 nucleotides downstream from the consecutive T residue termination site resulted in only a slight reduction in functional tRNA expression. In in vivo competition studies, the -18 deletion clone was less able to compete out the activity of a second suppressor tRNA gene than was the wild-type corresponding gene, suggesting that the upstream region plays a role in the formation of active transcription complexes in vivo. These results imply that the human serine tRNA gene contains an upstream regulatory region located between positions -66 and -18 that plays a positive role in modulating expression of this gene in vivo.

Base Sequence↗
PubMed1994

Reconstitution of cultured intestinal epithelial monolayers with a mucosal-derived T lymphocyte cell line. Modulation of epithelial phenotype dependent on lymphocyte-basolateral membrane apposition.

In vivo, epithelial cells which line the intestine are intimately associated with lymphocytes, termed intraepithelial lymphocytes. Previous studies have demonstrated that intraepithelial lymphocytes are present in the uninflamed mucosa, and become especially prominent in various human enteropathies including coeliac disease, tropical sprue, dermatitis herpetiformis, and giardiasis. Using the intestinal crypt cell line T84, and a previously well-defined human mucosa-derived lymphocyte (MDL) line with phenotypic features similar to (but not specific for) intraepithelial lymphocytes, we describe a co-culture model to study the functional sequellae of MDL-T84 cell interactions in vitro. A co-culture method was defined which permitted reconstitution of the paracellular spaces of physiologically confluent epithelial monolayers with MDL. Such co-cultures thus mimicked the correct geometry of intraepithelial lymphocytes-epithelial cell interactions. The presence of physiologically positioned MDL brought about specific and dramatic effects on intestinal epithelial monolayer function. In a dose-dependent fashion, the presence of MDL significantly attenuated barrier function (expressed as a decrease in monolayer resistance), decreased epithelial electrogenic Cl- secretion, and modulated epithelial-neutrophil interactions. Such effects were not reproduced in monolayers similarly reconstituted with inert polystyrene beads equivalent in size to MDL. These MDL-elicited effects on epithelial function specifically required direct MDL apposition to the epithelial basolateral membrane. Furthermore, this specific form of MDL-epithelial basolateral contact released soluble factors which were able to confer the MDL-reconstituted phenotype on virgin epithelial monolayers in the absence of MDL. We have previously shown that many aspects of the MDL converted epithelial phenotype described here can be induced by IFN-gamma. While IFN-gamma, a cytokine produced by many lymphocytes including intraepithelial lymphocytes, was detectable in conditioned supernatants from co-cultures, it existed at concentrations insufficient to fully explain the physiologic effects observed here.

Cells, Cultured↗
PubMed2005

Genetic modulation of senescent phenotypes in Homo sapiens.

Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or "normative" aging. These can be divided into two classes--those that have their impacts upon multiple organs and tissues (segmental progeroid syndromes) and those that have their major impacts upon a single organ or tissue (unimodal progeroid syndromes). The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases. Research on the Werner syndrome and a surprising number of other progeroid syndromes support the importance of the maintenance of genomic stability as a partial antidote to aging. The prototypic examples of the latter are Alzheimer type dementias. The three gene products that cause rare autosomal-dominant early-onset varieties of these disorders all participate in the modulation of the beta amyloid precursor protein. They thus support the importance of the maintenance of proper protein processing and folding as a partial antidote to aging.

Aging↗
PubMed2006

Modulation of antigenic phenotype in cultured human osteoblast-like cells by FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma.

BACKGROUND/AIMS: Recent reports demonstrated that osteoblast-like cells can also exert activities directly associated with the immune system (cytokine synthesis, antigen presentation, phagocytosis and stimulation of T lymphocytes). The present study aimed to analyze the effect of Transforming growth factorbeta1 (TGFbeta1), Fibroblast growth factor basic (FGFb), Platelet-derived growth factor-BB (PDGF-BB), Interleukin-1beta (IL-1beta), Interleukin-2 (IL-2), Lipopolysaccharide (LPS) and Interferon-gamma (IFNgamma) on the expression on osteoblast-like cells of antigens involved in antigen presentation. METHODS: Flow cytometry was used to investigate whether the growth factors FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma modulate the expression on cultured human osteoblast-like cells of different antigens involved in antigen-presentation and T cell activation. RESULTS: TGFbeta1 treatment significantly reduced the expression of CD54 and CD86. IL-1beta treatment significantly enhanced the expression of CD54, CD86 and HLA-DR. LPS and IFNgamma treatments produced a major increase in CD54, CD80, CD86 and HLA-DR expression. Expression of these antigen-presenting molecules was not significantly modified by FGFb, PDGF-BB or IL-2 treatment.

Adult↗
PubMed2002

Proteolipid protein gene modulates viability and phenotype of neurons.

Overexpression or lack of expression of proteolipid protein (PLP) gene by oligodendrocytes causes axonal pathology. It is unclear whether dysfunction of the PLP gene mediates its effects directly on neurons or indirectly by abnormal formation of myelin sheaths. We performed experiments using cocultures and conditioned media (CM) to test the direct effect of PLP gene expression on neurons. Non-glial cell lines were stably transfected with PLP or DM20 (an alternate splice variant of PLP) cDNAs. Immunocytochemistry and enhanced green fluorescent protein expression showed that translated products were synthesized and inserted into the plasma membrane in proper conformation. The number of surviving dorsal root ganglion (DRG) neurons was significantly less than controls when cocultured for 5 d with PLP-expressing cells. The number of degenerating neurons increased in a dose-dependent manner corresponding to increasing numbers of PLP-expressing cells. However, the number of surviving DRG neurons cocultured with DM20-expressing cells was comparable to that of controls, indicating that PLP-specific products contributed to decreased neuron survival. When DRG neurons were cultured with CM from PLP- or DM20-expressing cells, significantly fewer neurons survived with CM of PLP- but not DM20-expressing cells. This suggests that secreted factors from PLP-expressing cells contribute to neuronal death. Increased neuronal death found with PLP-expressing cells cannot be attributed to density-dependent artifacts, because in each experiment the density of different cell lines was similar. This effect of CM may be mediated by a negative pH shift elicited from PLP but not DM20 expression. These results indicate that PLP gene products directly modulate neuron viability.

Animals↗
PubMed1998

Phenotypic and functional modulation of T cells in vivo by extrathymic T cells when T cells with MHC class II disparity were injected into athymic nude mice.

TCRhigh cells are generated by the mainstream of T cell differentiation in the thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in the liver and by an alternative intrathymic pathway. It is still unknown how these T cell populations interact in vivo with each other. To investigate the interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude (B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated nude mice permitted a full expansion of TCRhigh cells which expressed the IL-2Ralpha+beta+ phenotype, namely, they were at the most activated state. These mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor origin and such TCRhigh cells continued to have the IL-2Ralpha(+/-)beta+ phenotype. These mice could survive but showed signs of chronic GVHD thereafter. In both situations, CD4+alphabeta T cells expanded irrespective of donor or recipient origin. These results suggest that TCRint cells in the recipient mice possess a regulatory function in relation to donor TCRhigh cells; as a result, fully activated TCRhigh cells acquired the IL-2Ralpha+beta+ phenotype and injured the host, but TCRhigh cells suppressed in vivo remained as the IL-2Ralpha(+/-)beta+ phenotype and only partially injured the host.

Animals↗
PubMed1995

Skeletal muscle contraction modulates carbonic anhydrase phenotype in adult mouse dorsal root ganglion neurons.

Recently carbonic anhydrase (CA) activity was demonstrated in adult mammalian proprioceptive neurons of the lumbar dorsal root ganglion (DRG). To assess if neuron-target interactions govern the neuronal CA phenotype, we examined how various experimental procedures which modify the interactions of these neurons with their central and peripheral targets, affect mouse L5 lumbar DRG CA activity. In normal mice and under central disconnection, carbonic anhydrase activity was detected in 30% of neurons. One day after sciatic nerve transaction the percentage of CA-positive neurons decreased to around 50% of that in controls, although both the total number of neurons per ganglion and glial CA content were unchanged. The pattern of CA activity then remained stable until at least 30 days post-operative. All experimental procedures used to block muscle contraction, including ventral rhizotomy, tenotomy, local application to the nerve of both tetrodotoxin and lidocaine or intramuscular injection of the botulinum toxin, produced a significant decrease in neuronal CA staining. Moreover, axonal transport block by vinblastine induced a decrease in CA-positive neurons. These results show that functional neuron-muscle interactions independent of DRG-spinal Cord influences contribute to the regulation of CA activity in lumbar DRG neurons. This modulation could be under the control of unidentified activity-dependent molecular mechanism involving stimuli through the skeletal muscle contraction, inducing in turn, the synthesis of a CA-regulating factor(s) retrogradely transported to the neuronal cell body and/or nuclei.

Animals↗
PubMed1993

Pilus-facilitated adherence of Neisseria meningitidis to human epithelial and endothelial cells: modulation of adherence phenotype occurs concurrently with changes in primary amino acid sequence and the glycosylation status of pilin.

Adherence of capsulate Neisseria meningitidis to endothelial and epithelial cells is facilitated in variants that express pili. Whereas piliated variants of N. meningitidis strain C311 adhered to endothelial cells in large numbers (> 150 bacteria/cell), derivatives containing specific mutations that disrupt pilE encoding the pilin subunit were both non-piliated and failed to adhere to endothelial cells (< 1 bacterium/cell). In addition, meningococcal pili recognized human endothelial and epithelial cells but not cells originating from other animals. Variants of strain C311 were obtained that expressed pilins of reduced apparent M(r) and exhibited a marked increase in adherence to epithelial cells. Structural analysis of pilins from two hyper-adherent variants and the parent strain were carried out by DNA sequencing of their pilE genes. Deduced molecular weights of pilins were considerably lower compared with their apparent M(r) values on SDS-PAGE. Hyper-adherent pilins shared unique changes in sequence including substitution of Asn-113 for Asp-113 and changes from Asn-Asp-Thr-Asp to Thr-Asp-Ala-Lys at residues 127-130 in mature pilin. Asn residues 113 and 127 of 'parental' pilin both form part of the typical eukaryotic N-glycosylation motif Asn-X-Ser/Thr and could potentially be glycosylated post-translationally. The presence of carbohydrate on pilin was demonstrated and when pilins were deglycosylated, their migration on SDS-PAGE increased, supporting the notion that variable glycosylation accounts for discrepancies in apparent and deduced molecular weights. Functionally distinct pilins produced by two fully piliated variants of a second strain (MC58) differed only in that the putative glycosylation motif Asn-60-Asn-61-Thr-62 in an adherent variant was replaced with Asp-60-Asn-61-Ser-62 in a non-adherent variant. Fully adherent backswitchers obtained from the non-adherent variant always regained Asn-60 but retained Ser-62. We propose, therefore, that functional variations in N. meningitidis pili may be modulated in large part by primary amino acid sequence changes that ablate or create N-linked glycosylation sites on the pilin subunit.

Amino Acid Sequence↗
PubMed2006

Human plasmacytoid dendritic cell function: inhibition of IFN-alpha secretion and modulation of immune phenotype by vasoactive intestinal peptide.

Plasmacytoid dendritic cells (PDC) are considered the main sentinels against viral infections and play a major role in immune tolerance. Vasoactive intestinal peptide (VIP) is a potent immunomodulator, whose role in PDC function is unknown. The present study was designed to investigate whether human PDC express VIP receptors and whether VIP has immunological effects on PDC. Using real-time RT-PCR and immunofluorescence, we demonstrated that VIP receptors VPAC1 and VPAC2 are expressed on PDC. After culturing PDC with VIP and CpG oligodeoxynucleotides for 48 h, expression of surface molecules with significance for PDC-T cell interactions as well as IFN-alpha secretion were quantified using FACS analysis and ELISA, respectively. For functional assays, CFSE-stained CD4+ T cells were coincubated with differentially treated PDC. T cell proliferation and production of various cytokines were determined by FACS analysis and ELISA. VIP enhanced PDC expression of CD86, MHC II, and CCR7. In contrast, VIP inhibited PDC secretion of IFN-alpha and expression of Neuropilin-1 and MHC I. The potential of CpG oligodeoxynucleotide-activated PDC to induce proliferation of allogeneic CD4(+) T cells was impaired when VIP was present during activation. Furthermore, pretreatment of PDC with VIP resulted in a decrease of the IFN-gamma:IL-4 ratio in cocultured T cells, suggesting a modulation of the immune response toward Th2. Taken together, these results strongly suggest that VIP regulates the immunological function of human PDC. VIP may thus be involved in the modulation of immune responses to viral infections as well as in the maintenance of immune tolerance.

CD4-Positive T-Lymphocytes↗
PubMed1984

Stability of collagen phenotype in morphologically modulated rabbit corneal endothelial cells.

Primary monolayer cultures of rabbit corneal endothelial cells maintained characteristic polygonal morphology and synthesized type IV collagen as a major collagenous peptide. Upon serial passage, [3H]-proline incorporation into proteins gradually decreased from the secondary subculture to a low of 71% of that in the primary culture in the fourth subculture, while type IV collagen synthesis significantly decreased from the tertiary subculture, and the fourth subculture retained only 22% of the primary culture value. When collagen molecules synthesized by the fourth subculture progeny were analyzed by SDS electrophoresis, no alteration was noted. The fourth subculture progeny continued to synthesize the characteristic type IV collagen, which migrates slightly faster than the beta 12 (I) band on SDS electrophoresis. However, the cellular morphology was changed dramatically from the characteristic polygonal shape to enlarged cells in the fourth subculture and mitotic activity was no longer apparent. Immunofluorescence studies showed that the enlarged fourth subculture progeny stained with anti-IV collagen antibodies, as did the primary polygonal endothelial cells. These findings confirmed type IV collagen synthesis in the enlarged endothelial cells. In addition, the morphologically altered cells continuously deposited Descemet's membrane-like extracellular matrices between the basal cell layer and the plastic substratum. These results suggest that endothelial cells lose their proliferative capacity as they age, but compensate for the loss of cell numbers by enlargement while maintaining a normal collagen phenotype.

Animals↗