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4 results on '"MESH : Amnion"'

1. Fresh and in vitro osteodifferentiated human amniotic membrane, alone or associated with an additional scaffold, does not induce ectopic bone formation in Balb/c mice

Author

Florelle Gindraux, C. Meyer, Aurélie Nallet, Pierre Layrolle, R. Laurent, Benoit de Billy, Laurence Nicod, Narcisse Zwetyenga, Laurent Obert, Service de chirurgie pédiatrique [CHU Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), NOVOTEC (Lyon), Structure fédérative de recherche : Ingénierie et biologie cellulaire et tissulaire (Université de Franche-Comté) ( SFR FED 4234 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Nanomédecine, imagerie, thérapeutique - UFC ( NIT / NANOMEDECINE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de Chirurgie Orthopédique Traumatologique et Plastique [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Service de Chirurgie Maxillo-Faciale et Stomatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service Chirurgie Maxillo-Faciale - Stomatologie - Chirurgie Plastique Réparatrice et Esthétique - Chirurgie de la main (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), NOVOTEC, Structure fédérative de recherche : Ingénierie et biologie cellulaire et tissulaire (Université de Franche-Comté) (SFR FED 4234), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Nanomédecine, imagerie, thérapeutique - UFC (EA 4662) (NIT / NANOMEDECINE), Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
0301 basic medicine, Cell Culture Techniques, 02 engineering and technology, MESH : Tissue Scaffolds, Mice, Osteogenesis, MESH: Tissue Scaffolds, MESH : Osteogenesis, MESH: Animals, MESH : Female, MESH: Osteogenesis, Immune reaction, Osteogenic potential, Cells, Cultured, Mice, Inbred BALB C, Tissue Scaffolds, biology, Chemistry, food and beverages, Cell Differentiation, MESH : Bone Substitutes, Ectopic, Cell biology, MESH : Amnion, Female, Biocompatibility, Stem cell, MESH : Cell Differentiation, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH : Cell Culture Techniques, MESH : Mesenchymal Stem Cell Transplantation, 0206 medical engineering, Biomedical Engineering, MESH: Mice, Inbred BALB C, MESH: Bone Substitutes, Bone healing, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mesenchymal Stem Cell Transplantation, BALB/c, Biomaterials, 03 medical and health sciences, In vivo, MESH : Cells, Cultured, Animals, Humans, MESH: Mesenchymal Stem Cell Transplantation, Amnion, MESH: Amnion, Bone, MESH : Mice, Inbred BALB C, Transplantation, MESH: Cell Culture Techniques, MESH: Humans, MESH : Mesenchymal Stromal Cells, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Mesenchymal stem cell, MESH : Humans, Mesenchymal Stem Cells, Cell Biology, biology.organism_classification, 020601 biomedical engineering, In vitro, 030104 developmental biology, Cell culture, Bone Substitutes, Immunology, MESH: Mesenchymal Stromal Cells, MESH : Animals, MESH: Female
Abstract

IF 1.331; International audience; The human amniotic membrane (hAM) has been successfully used as a natural carrier containing amniotic mesenchymal stromal cells, epithelial cells and growth factors. It has a little or no immunogenicity, and possesses useful anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. It has been used for many years in several indications for soft tissue repair. We previously reported that hAM represents a natural and preformed sheet containing highly potent stem cells, and could thus be used for bone repair. Indeed, native hAM possesses pre-osteoblastic potential that can easily be stimulated, even as far as mineralization, by means of in vitro osteogenic culture. However, cell culture induces damage to the tissue, as well as to cell phenotype and function. The aim of this study was to evaluate new bone formation by fresh and in vitro osteodifferentiated hAM, alone or associated with an additional scaffold presenting osteoinductive properties. Moreover, we also aimed to determine the effect of in vitro hAM pre-osteodifferentiation on its in vivo biocompatibility/tissue degradation. Results showed that neither fresh nor osteodifferentiated hAM induced ectopic bone formation, whether or not it was associated with the osteoinductive scaffold. Secondly, fresh and osteodifferentiated hAM presented similar in vivo tissue degradation, suggesting that in vitro hAM pre-osteodifferentiation did not influence its in vivo biocompatibility.

Published
2017

2. Use of amniotic membrane transplantation in the treatment of venous leg ulcers

Author

Didier Riethmuller, J M Sainthillier, Philippe Humbert, Carole Malugani, Isabelle Mermet, Stéphane Maddens, Nathalie Pottier, François Aubin, Sandrive Cairey-Remonnay, Pierre Tiberghien, Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Cell and Tissue Engineering Department, Etablissement Français du Sang de Bourgogne-Franche-Comté, Laboratoire d'Ingénierie et Biologie Cutanées ( LIBC ), IFR33-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire d'Ingénierie et Biologie Cutanées (LIBC), IFR33-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Saas, Philippe

Subjects
Male, MESH : Aged, MESH : Prospective Studies, MESH : Wound Healing, MESH: Pain Measurement, 030207 dermatology & venereal diseases, MESH: Aged, 80 and over, 0302 clinical medicine, Fibrosis, Medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH : Pain Measurement, Prospective Studies, MESH: Pain, Postoperative, Prospective cohort study, Pain Measurement, MESH: Aged, Aged, 80 and over, Pain, Postoperative, Biological Dressings, MESH : Pain, Postoperative, MESH: Varicose Ulcer, Granulation tissue, MESH: Granulation Tissue, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Ambulatory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Amnion, Female, MESH : Biological Dressings, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Dermatology, Placental Membrane, MESH : Granulation Tissue, Varicose Ulcer, 03 medical and health sciences, Humans, Amnion, MESH: Amnion, Adverse effect, MESH : Aged, 80 and over, Aged, Wound Healing, MESH: Humans, business.industry, MESH : Humans, medicine.disease, MESH: Prospective Studies, MESH: Male, Surgery, Transplantation, MESH: Wound Healing, MESH : Varicose Ulcer, Granulation Tissue, business, Wound healing, MESH: Female, MESH: Biological Dressings
Abstract

International audience; Amniotic membrane (AM), the most internal placental membrane, has unique properties including antiadhesive effects, bacteriostatic, wound protection and pain-reduction properties, as well as epithelialization initialization capacities. Furthermore, AM is widely available and less costly than other bioengineered skin substitutes. In a prospective pilot study, we evaluated the safety, feasibility, and the effects on healing of AM graft in 15 patients with chronic venous leg ulcers. AM grafts were prepared from placentas harvested during cesarean section. All grafted AM had adhered to the wound bed 7 days after being applied with a 100% engraftment rate. The percentage of granulation tissue increased significantly (from 17% on day 0 to 69% on day 14, p

Published
2007

3. Inflammation of choriodecidua induces tumor necrosis factor alpha-mediated apoptosis of human myometrial cells

Author

Leroy , Marie-Josèphe, Dallot , Emmanuelle, Czerkiewicz , Isabelle, Schmitz , Thomas, Breuiller-Fouché , Michelle, Breuiller-Fouche, Michelle, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]

Subjects
Lipopolysaccharides, Placenta, Extraembryonic Membranes, Apoptosis, MESH : Blotting, Western, Receptors, Tumor Necrosis Factor, MESH: Decidua, Pregnancy, MESH : Female, MESH : Inflamma, MESH: In Situ Nick-End Labeling, MESH : Culture Media, Conditioned, Cells, Cultured, MESH : Cell Nucleus, MESH : Cell Survival, MESH: Culture Media, Conditioned, MESH: Enzyme-Linked Immunosorbent Assay, MESH : Enzyme-Linked Immunosorbent Assay, MESH : Extraembryonic Membranes, MESH: Cell Survival, MESH : In Situ Nick-End Labeling, Myometrium, MESH : Amnion, Female, MESH: Cells, Cultured, MESH: Cell Nucleus, MESH : Decidua, Cell Survival, Blotting, Western, Enzyme-Linked Immunosorbent Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH : Cells, Cultured, MESH: Antibodies, Blocking, Decidua, In Situ Nick-End Labeling, Humans, MESH: Blotting, Western, Amnion, Antibodies, Blocking, MESH: Amnion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Nucleus, Inflammation, MESH: Inflamma, MESH : Antibodies, Blocking, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Tumor Necrosis Factor-alpha, MESH: Extraembryonic Membranes, MESH: Apoptosis, MESH : Humans, Toll-Like Receptor 4, Culture Media, Conditioned, MESH: Female, MESH : Apoptosis
Abstract

The present study investigated the ability of human choriodecidua to induce myometrial cell apoptosis through the secretion of tumor necrosis factor alpha (TNF). The secretion of TNF was evaluated in the culture supernatants of amnion and choriodecidua explants that were exposed to the bacterial endotoxin lipopolysaccharide (LPS) to mimic inflammation. The choriodecidua explants produced more TNF than the amnion explants in response to LPS stimulation, despite the fact that the choriodecidua had lower levels of TLR4 expression. Moreover, conditioned medium obtained from LPS-treated choriodecidua explants, but not that from amnion explants, decreased the number of viable cultured myometrial cells and induced cell apoptosis by inducing the overexpression of the proapoptotic protein BAX and by decreasing the expression of the anti-apoptotic protein BCL2. Neutralization of TNF in the choriodecidua-conditioned medium reversed this effect. Exogenous TNF mimicked LPS-treated choriodecidua-conditioned medium in that it induced myometrial cell apoptosis, reduced BCL2 expression, and increased BAX expression. Using neutralizing antibodies against both subtypes of TNF receptors, we found that only TNFRSF1A participates in TNF-induced myometrial cell apoptosis. Our in vitro model of LPS-induced inflammation of human fetal membrane explants suggests a mechanism by which TNF secreted by choriodecidua governs human myometrial cell apoptosis at the end of pregnancy. These data support the hypothesis that TNF participates in the complex network of signaling processes associated with uterine involution.

Published
2007

4. Evidence for a role of phosphodiesterase 4 in lipopolysaccharide-stimulated prostaglandin E2 production and matrix metalloproteinase-9 activity in human amniochorionic membranes

Author

Céline Méhats, Stéphanie Oger, Emmanuelle Dallot, Marie-Josèphe Leroy, Dominique Cabrol, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Leroy, Marie Josèphe, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH : Phosphodiesterase Inhibitors, medicine.medical_treatment, MESH: Adjuvants, Immunologic, Matrix metalloproteinase, MESH : Tissue Culture Techniques, MESH: Enzyme Precursors, MESH : Immune Sera, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Up-Regulation, MESH: Immune Sera, MESH : Up-Regulation, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH : Cyclic AMP, MESH: Dinoprostone, Phosphodiesterase, Chorion, Up-Regulation, 3. Good health, Cell biology, MESH: Membrane Proteins, medicine.medical_specialty, MESH: Enzyme Activation, MESH : Cyclooxygenase 2, Immunology, MESH: Prostaglandin-Endoperoxide Synthases, MESH: Chorion, Dinoprostone, Proinflammatory cytokine, 03 medical and health sciences, Adjuvants, Immunologic, MESH : 3',5'-Cyclic-Nucleotide Phosphodiesterase, Humans, Amnion, MESH: Humans, Tumor Necrosis Factor-alpha, Immune Sera, MESH : Humans, Cilomilast, MESH: Matrix Metalloproteinase 9, Enzyme Activation, MESH : Pregnancy, Endocrinology, MESH : Rolipram, chemistry, MESH : Membrane Proteins, 3',5'-Cyclic-AMP Phosphodiesterases, MESH: Tumor Necrosis Factor-alpha, MESH: Lipopolysaccharides, MESH: Female, Lipopolysaccharides, MESH: Interleukin-10, Lipopolysaccharide, Phosphodiesterase Inhibitors, MESH : Lipopolysaccharides, MESH: Phosphodiesterase Inhibitors, Tissue Culture Techniques, chemistry.chemical_compound, MESH: Rolipram, Cyclic AMP, Immunology and Allergy, MESH : Female, MESH : Matrix Metalloproteinase 9, Prostaglandin E2, MESH: Cyclic AMP, MESH : Tumor Necrosis Factor-alpha, Enzyme Precursors, MESH : Prostaglandin-Endoperoxide Synthases, MESH : Enzyme Precursors, Interleukin-10, Cytokine, Matrix Metalloproteinase 9, MESH : Amnion, Female, MESH: Cyclooxygenase 2, Rolipram, medicine.drug, MESH : Dinoprostone, MESH: 3',5'-Cyclic-Nucleotide Phosphodiesterase, Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH : Interleukin-10, Internal medicine, medicine, MESH: Tissue Culture Techniques, MESH: Amnion, 030304 developmental biology, Membrane Proteins, Cyclic Nucleotide Phosphodiesterases, Type 4, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH : Chorion, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, MESH : Adjuvants, Immunologic, MESH : Enzyme Activation
Abstract

Chorioamniotic infection is a leading cause of preterm premature rupture of fetal membranes (amnion and chorion). Bacterial infection induces an inflammatory response characterized by elevated production of proinflammatory cytokines; the latter activate the production of both PGs that stimulate uterine contractions, and matrix metalloproteinases (MMPs) that degrade the extracellular matrix of the chorioamniotic membranes. The inflammatory response is under the control of cAMP content, which is partly regulated by phosphodiesterases (PDE). In this study, we investigated the role of the PDE4 family in the inflammatory process triggered by LPS in a model of amniochorionic explants. We found that PDE4 family is the major cAMP-PDE expressed in human fetal membranes and that PDE4 activity is increased by LPS treatment. Selective inhibition of PDE4 activity affected LPS signaling, because PDE4 inhibitors (rolipram and/or cilomilast) reduced the release of the proinflammatory cytokine TNF-α and increased the release of the anti-inflammatory cytokine IL-10. PDE4 inhibition reduced cyclooxygenase-2 protein expression and PGE2 production and also modulated MMP-9, a key mediator of the membrane rupture process, by inhibiting pro-MMP-9 mRNA expression and pro-MMP-9 activity. These results demonstrate that the PDE4 family participates in the regulation of the inflammatory response associated with fetal membrane rupture during infection. The PDE4 family may be an appropriate pharmacological target for the management of infection-induced preterm delivery.

Published
2005

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