All-trans retinoic acid up-regulates Prostaglandin-E Synthase expression in human macrophages. 2012

Srinivas Mamidi, and Thomas P J Hofer, and Reinhard Hoffmann, and Löms Ziegler-Heitbrock, and Marion Frankenberger
Clinical Cooperation Group Inflammatory Lung Diseases (Helmholtz Zentrum München and Asklepios Fachkliniken Gauting) Gauting, Robert-Koch Allee 29, D-82131 Gauting, Germany.

All-trans retinoic acid (ATRA) is a potent retinoid, which has been used successfully in different clinical settings as a potential drug to treat COPD and emphysema. In the present study, we analyzed genes modulated by ATRA by performing mRNA expression array analysis on alveolar macrophages after treatment with ATRA. Here we observed a 375-fold up-regulation of Prostaglandin-E Synthase (microsomal PGES-1, NM_004878 PTGES) which mediates the conversion of prostaglandin H(2) (PGH(2)) to Prostaglandin E(2) (PGE(2)). We furthermore studied the expression of PTGES after treatment with ATRA in human monocyte-derived macrophages (MDMs) and bronchoalveolar lavage (BAL) cells. ATRA up-regulated PTGES mRNA expression in MDMs generated with M-CSF by 2500-fold whereas in M-CSF+IL-13 macrophages the up-regulation was only 20-fold. Similarly, ATRA up-regulated PTGES mRNA expression by factor 1524 in BAL cells. The up-regulation of PTGES mRNA expression by ATRA is both time and dose dependent. IL-13 suppressed the ATRA induced PTGES expression at both mRNA and protein level in MDM and BAL cells. We also observed that LPS acts synergistically with ATRA in MDMs and strongly induces PTGES expression. ATRA had little impact on cyclooxygenase-1 and -2 (COX-1 and -2) expression as compared to PTGES expression under the same experimental conditions. Furthermore, we observed an induction of PGE(2) levels by ATRA in BAL cells. These data indicate that ATRA is a potent inducer of PTGES expression in human macrophages but not in alternatively activated macrophages and suggest that the eicosanoid pathway is important for ATRA action in macrophages.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071876 Prostaglandin-E Synthases Oxidoreductases that catalyze the GLUTATHIONE-dependent oxidoreduction of PROSTAGLANDIN H2 to PROSTAGLANDIN E2. Cytosolic Prostaglandin E2 Synthase,Endoperoxide Isomerase,PGE2 Isomerase,PGE2 Synthase,PGR2 E-Isomerase,PTGES2 Protein,PTGES3 Protein,Prostaglandin E Isomerase,Prostaglandin E Synthase,Prostaglandin E Synthase 1,Prostaglandin E Synthase 2,Prostaglandin E Synthase 3,Prostaglandin E Synthase-1,Prostaglandin E Synthases,Prostaglandin E2 Synthase,Prostaglandin Endoperoxide E Isomerase,Prostaglandin H2 E-Isomerase,Prostaglandin H2-Prostaglandin E2 Isomerase,Prostaglandin R2 E-Isomerase,Prostaglandin-E Synthase,E Synthases, Prostaglandin,Isomerase, Endoperoxide,Isomerase, PGE2,Isomerase, Prostaglandin E,PGR2 E Isomerase,Prostaglandin H2 E Isomerase,Prostaglandin H2 Prostaglandin E2 Isomerase,Prostaglandin R2 E Isomerase,Synthase, PGE2,Synthase, Prostaglandin E,Synthase, Prostaglandin E2,Synthase, Prostaglandin-E,Synthases, Prostaglandin E,Synthases, Prostaglandin-E
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014212 Tretinoin An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). Retinoic Acid,Vitamin A Acid,Retin-A,Tretinoin Potassium Salt,Tretinoin Sodium Salt,Tretinoin Zinc Salt,Vesanoid,all-trans-Retinoic Acid,beta-all-trans-Retinoic Acid,trans-Retinoic Acid,Acid, Retinoic,Acid, Vitamin A,Acid, all-trans-Retinoic,Acid, beta-all-trans-Retinoic,Acid, trans-Retinoic,Potassium Salt, Tretinoin,Retin A,Salt, Tretinoin Potassium,Salt, Tretinoin Sodium,Salt, Tretinoin Zinc,Sodium Salt, Tretinoin,Zinc Salt, Tretinoin,all trans Retinoic Acid,beta all trans Retinoic Acid,trans Retinoic Acid

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