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D A Kniss

Publications and source records attributed to D A Kniss.

At least 19 recordsLinked to original sources
PubMed2006

Association of PAT proteins with lipid storage droplets in term fetal membranes.

As depots for neutral lipids, lipid storage droplets (LDs) accumulate with advancing gestation within the fetal membranes. Little is currently known about the proteins associated with the LDs of these cells. The PAT family [perilipin, adipose differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47)] represents a unique group of proteins thought to contribute to LD formation and function. We examined the association of each of the PAT proteins with LDs of term fetal membranes. We found that large LDs of amnion epithelial cells were reactive for neutral lipid stains and simultaneously encoated with ADRP and TIP47, but not perilipin. Within the remaining cell types, LDs were frequently co-labeled with antibodies recognizing ADRP and TIP47; however, in cells harboring only small LDs, the majority of TIP47 labeling was cytoplasmic. Structures labeled with perilipin antibodies were present only in chorion laeve trophoblasts. Gene and protein expression analyses suggested this to be a small molecular weight perilipin isoform, such as that seen in steroidogenic cells. We conclude that LDs are heterogeneous among differing cell types of the fetal membranes. Subclassification of LDs based on associated proteins suggests that these organelles may serve specialized functions within individual cells.

3T3 Cells↗
PubMed2006

Advanced techniques in placental biology -- workshop report.

Major advances in placental biology have been realized as new technologies have been developed and existing methods have been refined in many areas of biological research. Classical anatomy and whole-organ physiology tools once used to analyze placental structure and function have been supplanted by more sophisticated techniques adapted from molecular biology, proteomics, and computational biology and bioinformatics. In addition, significant refinements in morphological study of the placenta and its constituent cell types have improved our ability to assess form and function in highly integrated manner. To offer an overview of modern technologies used by investigators to study the placenta, this workshop: Advanced techniques in placental biology, assembled experts who discussed fundamental principles and real time examples of four separate methodologies. Y. Sadovsky presented the principles of microRNA function as an endogenous mechanism of gene regulation. J. Robinson demonstrated the utility of correlative microscopy in which light-level and transmission electron microscopy are combined to provide cellular and subcellular views of placental cells. A. Croy provided a lecture on the use of microdissection techniques which are invaluable for isolating very small subsets of cell types for molecular analysis. Finally, G. Rice presented an overview methods on profiling of complex protein mixtures within tissue and/or fluid samples that, when refined, will offer databases that will underpin a systems approach to modern trophoblast biology.

Animals↗
PubMed2006

Differentiation-dependent regulation of the cyclooxygenase cascade during adipogenesis suggests a complex role for prostaglandins.

AIM: A thorough understanding of the mechanisms of adipocyte differentiation and metabolism is important for the prevention and/or treatment of obesity and its complications, including type 2 diabetes mellitus. A complex role for prostaglandins (PGs) in adipogenesis is suggested. We examined the expression and cellular localization of enzymes in the cyclooxygenase (COX) cascade that synthesize PGs as well as the PG profile as a function of differentiation status in 3T3-L1 cells. METHODS: Murine 3T3-L1 preadipocytes were used as a model for studies of adipocyte differentiation induced by a hormone cocktail and compared with the parental fibroblastic line NIH 3T3. Both cell lines were incubated in maintenance medium or differentiation medium. Nine days after differentiation, the expression of enzymes in the COX cascade was evaluated by immunoblot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry, and PG formation was examined using enzyme immunoassay. RESULTS: A differentiation-dependent diminution of COX-1 and COX-2 mRNA and cognate proteins in 3T3-L1 cells was observed. PG release, including PGE(2), 6-keto PGF(1alpha), PGD(2) and 15d-PGJ(2), significantly decreased following differentiation in 3T3-L1 cells (anova/Tukey, p < 0.05). However, microsomal PGE synthase (mPGES) and lipocalin-type PGD synthase (L-PGDS) were selectively upregulated. Immunocytochemistry revealed that COX-1 and COX-2 became intracellularly more diffuse upon differentiation, whereas mPGES was redistributed to the nuclear compartment. CONCLUSIONS: Regulation of PG formation and COX-2 expression in 3T3-L1 cells is differentiation-dependent and involves changes in the levels of gene expression of the individual isoforms as well as redistribution of the enzymes within cellular compartments.

3T3-L1 Cells↗
PubMed2005

In situ immunolabeling allows for detailed localization of prostaglandin synthesizing enzymes within amnion epithelium.

Detailed information regarding the subcellular distribution of proteins within amnion epithelial cells is a goal of numerous placental biologists. In this report, we describe a versatile technique for in situ immunolabeling in amnion that is as technically permissible as traditional immunolabeling of cultured cells and, when coupled with confocal laser scanning microscopy, is similarly capable of providing detailed information regarding subcellular protein distribution. Using antibodies directed against sequential enzymes of the prostaglandin E biosynthesis cascade, we compared this novel method with immunofluorescent labeling using amnion cells in primary culture and cryosections of reflected fetal membrane rolls. By several criteria, we observed morphological variation between the cells cultured in vitro and the tissue specimens. Despite general consistencies in immunostaining patterns between the cryosectioned specimens and those labeled in situ, morphological preservation was superior using the latter technique. Relative to the cryosectioned specimens, in situ immunostaining was advantageous in that it permitted improved sampling efficiency, and allowed regional variations in labeling to be observed in a more global context within the tissue. Our results demonstrate that in situ immunolabeling provides a useful adjunct or alternative to immunolabeling using membrane roll preparations.

Amnion↗
PubMed2002

ED(27) trophoblast-like cells isolated from first-trimester chorionic villi are genetically identical to HeLa cells yet exhibit a distinct phenotype.

ED(27) trophoblast-like cells were prepared from human chorionic villus samples obtained at 9 weeks gestation and have been grown continuously in vitro without phenotypic drift for nearly a decade. These cells express many trophoblast markers, including cytokeratin, placental alkaline phosphatase (PLAP), secretion of 17beta-estradiol, and a microvillous apical surface. The ED(27) cell line is a useful model system for studies of placental cell biology and has been distributed to laboratories world-wide. However, experiments to investigate their relationship to primary villous cytotrophoblast have shown that these cells do not secrete detectable amounts of human chorionic gonadotropin in culture and, when digested with trypsin, disperse into individual cells. Furthermore, immunocytochemical studies demonstrated that, unlike villous cytotrophoblasts, ED(27) cells were immunoreactive with monoclonal antibodies recognizing some HLA Class I antigens. This was not HLA-G, however, as would be expected if these cells originated from extravillous cytotrophoblasts, but rather classical HLA-A, B which is thought not to be expressed by any trophoblast subpopulations. These inconsistencies prompted us to question the authenticity of the continuous cell line as it now exists. Genetic haplotype analysis using the polymerase chain reaction (PCR) revealed that ED(27) was genetically identically to the HeLa cell line. Inasmuch as HeLa cells have never been grown in the laboratory (DAK), the only possible origin of HeLa cell contamination of ED(27) cells was the WISH cell line, and further PCR analysis revealed that this cell line was also genetically identical to HeLa. Like ED(27) cells, HeLa cells and WISH cells synthesized small amounts of estrogen and were found to express PLAP and antigens recognized by the monoclonal antibodies ED822, directed against the syncytiotrophoblast, and J1B5 directed against villous cytotrophoblast. These results point out the need for adherence to rigorous and consistent quality control measures to assure the authenticity of cell lines used as in vitro model systems.

Adult↗
PubMed2001

Thermal compression and characterization of three-dimensional nonwoven PET matrices as tissue engineering scaffolds.

Nonwoven fibrous matrices have been widely used as scaffolds in tissue engineering, and modification of microstructure of these matrices is needed to organize cells in three-dimensional space with spatially balanced proliferation and differentiation required for functional tissue development. The method of thermal compression of nonwoven polyethylene terephthalate (PET) fabrics was developed and key parameters of temperature, pressure, and compression duration were evaluated in this study. The permanent deformation was obtained at elevated temperature under pressure and the viscoelastic compressional behaviors were observed, characterized by a distinct apparent modulus change in glass transition temperature region. A liquid extrusion method was further employed to analyze both pore size and its distribution for matrices with porosity ranging from 84 to 93%. It is also found that a more uniformly distributed pore size was resulted from thermal compression and the isotropic nature of nonwoven fabrics was preserved because of the proportional reduction of the pore by compression. The thermally compressed fabric matrices with two different pore sizes (15 and 20 microm in pore radius) were used to culture human trophoblast ED27 and NIH 3T3 cells. It was found that cells cultured in the different pore-size PET matrices had different cell spatial organization and proliferation rates. The smaller pores in the matrix allowed cells to spread better and proliferate faster, while cells in the larger pores tended to form large aggregates and had lower proliferation rate. The thermal compression technique also can be applied to other synthetic fibrous matrices including biodegradable polymers used in tissue engineering to modify the microstructure according to their viscoelastic properties.

3T3 Cells↗
PubMed2001

Blockade NF-kappaB activation prohibits TNF-alpha-induced cyclooxygenase-2 gene expression in ED27 trophoblast-like cells.

Among the many functions of trophoblast cells is the production of prostaglandins (PGs) for governing several fetoplacental vascular functions during gestation and the triggering of events leading to parturition. Recent evidence suggests that pro-inflammatory cytokines such as tumour necrosis factors (TNF-alpha) induce PG formation via cyclooxygenase-2 (COX-2), a highly inducible enzyme whose gene is regulated at least in part by inducible transcription factor NF-kappaB. To examine the mechanism by which COX-2-driven PG biosynthesis occurs in trophoblast cells, we utilized the immortalized trophoblast-like cell line ED(27). These cells exhibit many of the properties of villous or extravillous trophoblasts and produce large amounts of PGs in response to TNF-alpha. We demonstrated that challenge of ED(27)cells with TNF-alpha caused binding of the NF-kappaB complex to its kappaB site followed by increased accumulation of COX-2 transcripts. In addition, the inhibitor of NF-kappaB, IkappaB-alpha, became phosphorylated and was rapidly degraded in cytokine-treated cells; this process was abolished by co-incubation with the proteasome inhibitor, MG-132. Finally, when cells were pre-incubated with MG-132 and then challenged with TNF-alpha, PG formation was attenuated in a concentration-dependent manner. These data indicate that, in ED(27)trophoblast-like cells isolated from the first-trimester placenta, TNF-alpha treatment leads to activation of NF-kappaB and subsequent transcription of the COX-2 gene.

Adult↗
PubMed2001

Characterization of a TGFbeta-responsive human trophoblast-derived cell line.

The placenta is formed by developing trophoblast cells to facilitate fluid, gas and nutrient exchange with the mother. Inappropriate trophoblast responsiveness can lead to life threatening complications during pregnancy including intrauterine growth retardation, pre-eclampsia, spontaneous abortion and malignancy that could lead to fetal loss. Transforming growth factor beta (TGFbeta) is a multifunctional cytokine required for embryonic development and is an important regulator of human trophoblast function. Although TGFbeta is critical for placental and embryonic development, there are currently no established TGFbeta-responsive human trophoblast-derived cell lines available to study the mechanisms by which TGFbeta regulates trophoblast function. Our studies have examined the transformed human trophoblast-derived cell line, ED27, to determine if it is responsive to TGFbeta. Our data indicate that TGFbeta dose responsively and reversibly inhibits cell growth in ED27 cells and induces classic TGFbeta response genes, fibronectin and plasminogen activator inhibitor 1 (PAI-1). TGFbeta also induces an inhibitor of trophoblast invasion, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in ED27 cells. Our studies have identified a human trophoblast-derived cell line that parallels isolated primary human trophoblasts in their responses to TGFbeta. This cell line may provide us with the opportunity to determine TGFbeta-mediated responses on human trophoblast functions not previously possible.

Apoptosis↗
PubMed2001

Oxygen tension influences proliferation and differentiation in a tissue-engineered model of placental trophoblast-like cells.

A considerable oxygen gradient exists in vivo, which exerts regulatory effects on tissue development and function. The objective of this study was to evaluate the feasibility of controlling cell proliferation and differentiation by regulating oxygen tension in a tissue-engineered bioreactor model. The effects of oxygen tension on proliferation and differentiation of first-trimester human trophoblast cells (known as ED(27) cells) were studied in a fiber-bed perfusion bioreactor system in which cells were grown in polyethylene terephthalate (PET) nonwoven fibrous matrix. By varying the oxygen tension between 2% and 20%, differential responses of trophoblasts in their proliferation and differentiation activities were observed. There was no significant difference in the rates of glucose consumption and lactate production, and lactate dehydrogenase (LDH) level in the culture media for both 2% and 20% oxygen tension cultures, indicating that cell metabolic activities were not limited by low oxygen tension. However, 2% oxygen stimulated cell proliferation but impeded the secretion of a functional hormone, 17beta-estradiol. In contrast, 20% oxygen tension reduced cell proliferation, but yielded higher hormone secretion. A step change in oxygen tension from 2% to 20% caused cells in the bioreactor to increase 17beta-estradiol secretion and shifted cell cycle from proliferation to differentiation, which were verified with the expression levels of cyclin B1 and p27(kip1). However, no significant response to a change from 6% to 20% oxygen tension was observed. It is concluded that changes in oxygen tension can be an effective strategy to control cell cycle and long-term tissue development. This work also demonstrated the important role of oxygen tension in regulating placental trophoblast tissue development and the feasibility of using the bioreactor under well-controlled physiological environment for tissue engineering applications.

Bioreactors↗
PubMed2001

Three-dimensional cell-scaffold constructs promote efficient gene transfection: implications for cell-based gene therapy.

To date, introduction of gene-modified cells in vivo is still a critical limitation for cell-based gene therapy. In this study, based on tissue engineering techniques, we developed a three-dimensional (3-D) transfection system to be cell-based gene delivery vehicle. Human trophoblast-like ED(27) and fibroblastic NIH3T3 cells were used as model cell lines. Cells were seeded onto PET fibrous matrices and plated on polyethylene terephathalate (PET) films as 2-D transfection control. The cell-matrices and cell-films were transfected with pCMV-betagal and pEGFP (green fluorescent protein) reporter gene vectors using LipofectAmine reagent. Gene expression on 3-D versus 2-D growth surface were investigated. The effects of seeding method, seeding density, porosity of the PET matrix, and culturing time of the cell-matrix complex on cDNA transfection and expression in the 3-D cell-matrix complex were also investigated. The beta-gal assay and GFP detection showed that 3-D transfection promoted a higher gene expression level and longer expression time as compared to 2-D transfection. There existed an optimal initial cell seeding density for gene transfection of 3-D cell-matrix complex. Cells seeded on PET matrices with a lower porosity ( approximately 87%) had higher gene expression activities than cells in the matrices with a higher porosity ( approximately 90%). Also, Higher gene expression levels of beta-gal were obtained for the more uniformly seeded matrices that were seeded with a depth-filtration method. The results from this study demonstrate the potential utility of cells seeded onto 3-D fibrous matrices as cell-based gene delivery vehicle for in vitro study of gene expression or in vivo gene therapy.

3T3 Cells↗
PubMed2001

Human cord cell hematopoiesis in three-dimensional nonwoven fibrous matrices: in vitro simulation of the marrow microenvironment.

Current hematopoietic culture systems mainly utilize two-dimensional devices with limited ability to promote self-renewal of early progenitors. In vivo-like three-dimensional (3-D) culture environments might be conducive to regulating stem cell proliferation and differentiation similar to in vivo hematopoiesis. The few 3-D cultures reported in the literature either produced few progenitors or provided little information about microenvironment. In this study, we constructed a 3-D hematopoietic microenvironment composed of nonwoven matrix and human cord blood (CB) cells to simulate the marrow microenvironment and expand cord progenitors. Nonwoven polyethylene terephthalate (PET) fabric with defined microstructure was used as the 3-D scaffold and the PET surface was modified by hydrolysis to improve cell adhesion. Different cell organizations were formed in a 3-D matrix in a developmental manner, from individual cells and cells bridging between fibers to large cell aggregates. Both stromal and hematopoietic cells were distributed spatially within the scaffold. Compared to two-dimensional (2-D) CD34(+) cell culture, 3-D culture produced 30-100% higher total cells and progenitors without exogenous cytokines. With thrombopoietin and flt-3/flk-2 ligand, it supported two- to three-fold higher total cell number (62.1- vs. 24.6-fold), CD34(+) cell number (6.8- vs. 2.8-fold) and colony-forming unit (CFU) number for 7-9 weeks (n = 6), indicating a hematopoiesis pathway that promoted progenitor production. Culture in 3-D nonwoven matrices enhanced cell-cell and cell-matrix interactions and allowed 3-D distribution of stromal and hematopoietic cells. The formation of cell aggregates and higher progenitor content indicated that the spatial microenvironment in 3-D culture played an important role in promoting hematopoiesis. This 3-D culture system can be used as an in vitro model to study stem cell or progenitor behavior, and to achieve sustained progenitor expansion.

Biocompatible Materials↗
PubMed2000

Effects of pore size in 3-D fibrous matrix on human trophoblast tissue development.

The effects of pore size in a 3-D polyethylene terephthalate (PET) nonwoven fibrous matrix on long-term tissue development of human trophoblast ED27 cells were studied. Thermal compression was used to modify the porosity and pore size of the PET matrix. The pore size distributions in PET matrices were quantified using a liquid extrusion method. Cell metabolic activities, estradiol production, and cell proliferation and differentiation were studied for ED27 cells cultured in the thermally compressed PET matrices with known pore structure characteristics. In general, metabolic activities and proliferation rate were higher initially for cultures grown in the low-porosity (LP) PET matrix (porosity of 0.849, average pore size of 30 microm in diameter) than those in the high-porosity (HP) matrix (porosity of 0.896, average pore size of 39 microm in diameter). However, 17beta-estradiol production and cell differentiation activity in the HP matrix surpassed those in the LP matrix after 12 days. The expression levels of cyclin B1 and p27kip1 in cells revealed progressively decreasing proliferation and increasing differentiation activities for cells grown in PET matrices. Also, difference in pore size controlled the cell spatial organization in the PET matrices and contributed to the tissue development in varying degrees of proliferation and differentiation. It was also found that cells grown on the 2-D surface behaved differently in cell cycle progression and did not show increased differentiation activities after growth had stopped and proliferation activities had lowered to a minimal level. The results from this study suggest that the 3-D cell organization guided by the tissue scaffold is important to tissue formation in vitro.

Blotting, Western↗
PubMed1999

Blockade of nitric oxide formation down-regulates cyclooxygenase-2 and decreases PGE2 biosynthesis in macrophages.

Elevated levels of nitric oxide (NO*) produced by expression of inducible nitric oxide synthase (iNOS/NOS type 2) and high levels of prostaglandins (PGs) generated by expression of inducible cyclooxygenase (COX-2/PGH2 synthase-2) are important mediators of immune and inflammatory responses. Previous studies have shown that endogenous levels of NO* can influence the formation of PGs. We examined the mechanism by which NO* regulates PG biosynthesis in macrophages. Treatment of a murine macrophage cell line (ANA-1) with lipopolysaccharide (LPS, 10 ng/mL) and interferon-gamma (IFN-gamma, 10 U/mL) for 20 h elicited high levels of nitrite (NO2-) and prostaglandin E2 (PGE2) that were inhibited in a dose-dependent fashion by the NOS inhibitor, aminoguanidine (AG), with IC50 values of 15.06 and 0.38 microM for NO2- and PGE2, respectively. Stimulation of cultures with LPS and IFN-gamma for 20 h induced de novo iNOS protein expression that was not altered by the addition of AG (0.1, 10, or 1000 microM). In contrast, treatment of cultures with LPS and IFN-gamma for 20 h promoted COX-2 mRNA and protein expression that were decreased in a dose-dependent fashion by AG (P < 0.05 with 10 and 1000 microM). LPS and IFN-gamma-induced COX-2 protein expression was not decreased in cultures treated with AG for 2 h, illustrating that AG does not inhibit the formation of COX-2 protein. Analysis of partially purified enzyme extracts demonstrated that AG did not directly inhibit the enzymatic activity of COX. Additional experiments revealed that NO* donors (S-nitroso-N-aceytl-D-L-pencillamine, SNAP, at 0.1, 10, and 1000 microM) did not induce de novo COX-2 protein expression or potentiate COX-2 expression in cells treated with LPS and/or IFN-gamma. Our results suggest that, while endogenous NO* is not required for de novo COX-2 mRNA and protein expression, NO* is necessary for maintaining prolonged COX-2 gene expression.

Animals↗
PubMed1999

Development of an in vitro human placenta model by the cultivation of human trophoblasts in a fiber-based bioreactor system.

The in vitro human trophoblast culture system is of significant importance in the study of human placenta development and its role as the transport organ between maternal and fetal circulations in normal physiology and pathology pregnancy. But conventional in vitro model systems fail to reproduce many important features of human placenta in vivo. In our study, a perfusion bioreactor system was developed with a chemically modified poly(ethylene terephthalate) (PET) fibrous matrix as the cell culture scaffold. The dual compartment design of the bioreactor simulates maternal and fetal circulation systems in vivo. First trimester human trophoblast cells readily attached on a chemically modified PET fiber surface. The detection of human fibronectin showed that cells were able to form three-dimensional structures by aggregation and bridging between fibers. Moreover, metabolic and hormone secretion data showed that cells in this perfusion culture system maintained their normal functional activities. The results of this study demonstrate the feasibility of tissue engineering human trophoblast cells in a perfusion bioreactor system for the development of an in vitro drug testing model system.

Biocompatible Materials↗
PubMed1999

Peroxisome proliferator-activated receptor gamma activation in human breast cancer.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family of ligand-activated transcription factors. This study was designed to evaluate ligand activation of PPARgamma in human breast cancer cells. DNA binding by endogenous PPARgamma in gel shift assays and activation of PPARgamma by prostanoid and thiazolidinedione ligands in reporter gene assays differed between the cell lines. The PPARgamma ligands elicited an anti-proliferative effect in MTT proliferation assays. Our data point to a variable, cell-specific response to different gamma-ligands, which holds significance for further studies on the role of PPARgamma in mediating breast cancer growth and progression.

Breast Neoplasms↗
PubMed1998

Regulation of parturition update. Endocrine and paracrine effectors of term and preterm labor.

This article summarizes the role of endocrine and paracrine mediators of human parturition. Gonadal steroids (17 beta--estradiol and progesterone) mediate many of the decidual and uterine contractile functions during early events in labor. Proinflammatory cytokines and chemokines orchestrate many of the events triggering or sustaining active labor at term and in the preterm setting. Several autacoids (prostaglandins, platelet-activating factor) serve proximal activities such as uterine contractility and remodeling of the cervical extracellular matrix leading to dilatation and effacement. As the biochemical participants during parturition become more clearly understood, it will be possible to develop improved surveillance, management, and treatment strategies for preterm labor.

Autacoids↗
PubMed1997

Rapid and transient induction of cyclo-oxygenase 2 by epidermal growth factor in human amnion-derived WISH cells.

The central enzyme in the prostaglandin (PG) biosynthetic cascade is PGH2 synthase or cyclo-oxygenase (COX). At present, two distinct isoforms of PGH2 synthase/COX have been identified: COX-1 and COX-2. In many systems, COX-1 is a constitutively expressed isoform that is responsible for normal physiological production of PGs, whereas COX-2 is an inducible isoform that responds to cytokines, endotoxin and growth factors by producing high levels of PGs. The regulation of COX-2 mRNA and protein, and the subsequent production of PGE2, were therefore examined in amnion-derived WISH cells stimulated with epidermal growth factor (EGF). Treatment of WISH cells with EGF (0.01-100 ng/ml) elicited dose-dependent synthesis of COX-2 mRNA and protein de novo. In addition, stimulation of WISH cells with EGF (10 ng/ml) induced steady-state levels of COX-2 mRNA and protein that appeared within 30 min and then declined rapidly to near baseline levels within 2-4 h. In contrast, COX-1 protein was unchanged in response to treatment with EGF. PGE2 production was also rapid and transient. Preincubation of cells with the novel COX-2 enzymic inhibitor NS-398 (10(-5)-10(-10) M) completely prevented PGE2 formation in a dose-dependent manner. Preincubation of cells in dexamethasone (Dex; 0.1 microM), however, resulted in only a 31% decrease in PGE2 formation in response to EGF (10 ng/ml) while completely attenuating PGE2 biosynthesis in tumour necrosis factor alpha (TNF-alpha)-stimulated cells. In addition, Dex (0.1 microM) was only partly effective at preventing EGF-induced COX-2 mRNA and protein expression de novo, whereas Dex completely inhibited TNF-alpha-promoted COX-2 mRNA and protein expression. Thus the results presented here demonstrate that EGF induces the rapid but transient expression of COX-2 mRNA and protein and the subsequent production of PGE2 in WISH cells.

Amnion↗