![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 58, Issue 4, 701-708, October 2000
Department of Pharmacology, Emory University School of Medicine
(A.M.R., K.X., M.L.E., T.J.M.), and the Program in Molecular and
Systems Pharmacology, Graduate Division of Biological and Biomedical
Sciences, Emory University (A.M.R., T.J.M.), Atlanta, Georgia
The prostaglandin synthase cyclooxygenase-2 (COX-2) is produced by an
immediate early response gene induced in most cells by a variety of
stimuli. Several studies have shown that the immunosuppressant cyclosporin (CsA) interferes with prostanoid metabolism, but the mechanisms are unclear. Here we examine the effect of CsA on COX-2 mRNA
induction in cultured rat vascular smooth muscle cells (VSMC) that
natively express the nuclear factor of activated T-cells, a known
mediator of CsA-sensitive transcription. CsA significantly suppresses
strong COX-2 mRNA induction caused by the Ca2+-mobilizing
mitogens UTP, angiotensin II, and platelet-derived growth factor-BB,
and the synergistic induction caused by costimulation with ionomycin
and a phorbol ester. Forskolin and interleukin-1
are substantially
weaker COX-2 mRNA inducers, and CsA does not inhibit their effect. CsA
strongly inhibits UTP-, angiotensin II-, and platelet-derived growth
factor-BB-stimulated COX-2 gene transcription as measured by nuclear
run-on or promoter-reporter studies, but has no effect on mRNA
induction caused by post-transcriptional stabilization of a distal
COX-2 mRNA 3'-untranslated region regulatory element. These data show
that CsA selectively inhibits mitogen-induced COX-2 gene expression by
a transcriptional mechanism that may involve the nuclear factor of
activated T-cells.
This article has been cited by other articles:
|
|
 |
|
  M.-R. Du, W.-H. Zhou, L. Dong, X.-Y. Zhu, Y.-Y. He, J.-Y. Yang, and D.-J. Li Cyclosporin A Promotes Growth and Invasiveness In Vitro of Human First-Trimester Trophoblast Cells Via MAPK3/MAPK1-Mediated AP1 and Ca2+/Calcineurin/NFAT Signaling Pathways Biol Reprod, June 1, 2008; 78(6): 1102 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Xu, C. M. Kitchen, H.-K. G. Shu, and T. J. Murphy Platelet-derived Growth Factor-induced Stabilization of Cyclooxygenase 2 mRNA in Rat Smooth Muscle Cells Requires the c-Src Family of Protein-tyrosine Kinases J. Biol. Chem., November 9, 2007; 282(45): 32699 - 32709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Jackson, Y. M. Usachev, and S. A. Thayer Bradykinin-Induced Nuclear Factor of Activated T-Cells-Dependent Transcription in Rat Dorsal Root Ganglion Neurons Mol. Pharmacol., August 1, 2007; 72(2): 303 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zhang, P. Hopwood, C. C. Abrams, A. Downing, F. Murray, R. Talbot, A. Archibald, S. Lowden, and L. K. Dixon Macrophage Transcriptional Responses following In Vitro Infection with a Highly Virulent African Swine Fever Virus Isolate. J. Virol., November 1, 2006; 80(21): 10514 - 10521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Peavy, K. B. Hubbard, A. Lau, R. B. Fields, K. Xu, C. J. Lee, T. T. Lee, K. Gernert, T. J. Murphy, and J. R. Hepler Differential Effects of Gq{alpha}, G14{alpha}, and G15{alpha} on Vascular Smooth Muscle Cell Survival and Gene Expression Profiles Mol. Pharmacol., June 1, 2005; 67(6): 2102 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Damirin, H. Tomura, M. Komachi, M. Tobo, K. Sato, C. Mogi, H. Nochi, K. Tamoto, and F. Okajima Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I2 Pathway in Human Coronary Artery Smooth Muscle Cells Mol. Pharmacol., April 1, 2005; 67(4): 1177 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Duque, M. Fresno, and M. A. Iniguez Expression and Function of the Nuclear Factor of Activated T Cells in Colon Carcinoma Cells: INVOLVEMENT IN THE REGULATION OF CYCLOOXYGENASE-2 J. Biol. Chem., March 11, 2005; 280(10): 8686 - 8693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vila-del Sol and M. Fresno Involvement of TNF and NF-{kappa}B in the Transcriptional Control of Cyclooxygenase-2 Expression by IFN-{gamma} in Macrophages J. Immunol., March 1, 2005; 174(5): 2825 - 2833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-E. Janelle, A. Gravel, J. Gosselin, M. J. Tremblay, and L. Flamand Activation of Monocyte Cyclooxygenase-2 Gene Expression by Human Herpesvirus 6. ROLE FOR CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN AND ACTIVATOR PROTEIN-1 J. Biol. Chem., August 16, 2002; 277(34): 30665 - 30674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Abbott, J. R. Loss II, A. M. Robida, and T. J. Murphy Evidence That Galpha q-Coupled Receptor-Induced Interleukin-6 mRNA in Vascular Smooth Muscle Cells Involves the Nuclear Factor of Activated T Cells Mol. Pharmacol., November 1, 2000; 58(5): 946 - 953. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
