Dexamethasone differentially affects interleukin 1 beta- and cyclic AMP-induced nitric oxide synthase mRNA expression in renal mesangial cells. 1994

D Kunz, and G Walker, and J Pfeilschifter
Department of Pharmacology, Biozentrum, University of Basel, Switzerland.

Inducible nitric oxide synthase (iNOS) is expressed in renal mesangial cells in response to two principal classes of activating signals that interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin (IL)-1 beta or tumour necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP). We examined whether dexamethasone differentially affects iNOS induction in response to IL-1 beta and a membrane-permeable cAMP analogue, N6,O-2'-dibutyryladenosine 3',5'-phosphate (Bt2cAMP). Nanomolar concentrations of dexamethasone suppress IL-1 beta- as well as Bt2cAMP-induced iNOS protein expression and production of nitrite, the stable end product of nitric oxide (NO) formation. In contrast, dexamethasone prevents induction of iNOS mRNA in response to Bt2cAMP without affecting IL-1 beta-triggered increase in iNOS mRNA levels. These data suggest that dexamethasone acts at different levels, depending on the stimulus used to suppress iNOS induction in mesangial cells.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
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
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D003994 Bucladesine A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed) Dibutyryl Adenosine-3',5'-Monophosphate,Dibutyryl Cyclic AMP,(But)(2) cAMP,Bucladesine, Barium (1:1) Salt,Bucladesine, Disodium Salt,Bucladesine, Monosodium Salt,Bucladesine, Sodium Salt,DBcAMP,Dibutyryl Adenosine 3,5 Monophosphate,N',O'-Dibutyryl-cAMP,N(6),0(2')-Dibutyryl Cyclic AMP,AMP, Dibutyryl Cyclic,Adenosine-3',5'-Monophosphate, Dibutyryl,Cyclic AMP, Dibutyryl,Dibutyryl Adenosine 3',5' Monophosphate,Disodium Salt Bucladesine,Monosodium Salt Bucladesine,N',O' Dibutyryl cAMP,Sodium Salt Bucladesine
D005920 Glomerular Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX. Mesangium, Glomerular,Mesangial Extracellular Matrix,Extracellular Matrices, Mesangial,Extracellular Matrix, Mesangial,Glomerular Mesangiums,Matrices, Mesangial Extracellular,Matrix, Mesangial Extracellular,Mesangial Extracellular Matrices,Mesangiums, Glomerular
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000594 Amino Acid Oxidoreductases A class of enzymes that catalyze oxidation-reduction reactions of amino acids. Acid Oxidoreductases, Amino,Oxidoreductases, Amino Acid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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