In Vitro Effects of VA441, a New Selective Cyclooxygenase-2 Inhibitor, on Human Osteoarthritic Chondrocytes exposed to IL-1<I>β</I>
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概要
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The aim of this in vitro study was to examine the possible effect of [2-methyl-5-(4-methylsulphonyl)phenyl-1-phenyl-3-(2-<I>n</I>-propyloxyethyl)]-1<I>H</I>-pyrrole (VA441), a new selective cyclooxygenase (COX)-2 inhibitor, on human osteoarthritic (OA) chondrocyte cultivated in the presence or absence of interleukin-1<I>β</I> (IL-1<I>β</I>). In particular, we assessed the effects of 1 and 10 <I>μ</I>M of VA441, celecoxib, and indomethacin on cell viability, COX-2 and inducible nitric oxide synthase (iNOS) gene expression, prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) production, and nitric oxide (NO) and metalloproteinase-3 (MMP-3) release. Furthermore, we carried out morphological assessment by transmission electron microscopy (TEM). The presence of IL-1<I>β</I> led to a significant increase in PGE<SUB>2</SUB>, MMP-3, and NO production, as well as a significant increase in gene expression of COX-2 and iNOS. All the drugs tested had a statistically significant inhibitory effect on PGE<SUB>2</SUB> production and gene expression of COX-2 stimulated by IL-1<I>β</I>. VA441 and celecoxib significantly suppressed IL-1<I>β</I>-stimulated MMP-3 and NO and iNOS gene expression in a dose-dependent manner, while indomethacin did not show any significant effect on MMP-3 and NO production or on iNOS gene expression. TEM demonstrated that IL-1<I>β</I> severely alters the structure of chondrocytes; after co-incubation with VA441 or celecoxib, the cells recovered their ultrastructure. Our data suggest that VA441 and celecoxib may have a beneficial effect on chondrocyte metabolism.
著者
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CAPPELLI Andrea
Department of Pure and Applied Medicinal Chemistry, University of Siena
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Cappelli Andrea
Department of Pure and Applied Medicinal Chemistry, University of Siena, Italy
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FIORAVANTI Antonella
Department of Clinical Medicine and Immunology, Rheumatology Unit
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TINTI Laura
Department of Clinical Medicine and Immunology, Rheumatology Unit
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PASCARELLI Nicola
Department of Clinical Medicine and Immunology, Rheumatology Unit
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LAMBOGLIA Antonello
Department of Clinical Medicine and Immunology, Rheumatology Unit
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BIAVA Mariangela
Department of Chemistry and Pharmaceutical Technology, University "La Sapienza"
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GIORDANI Antonio
Rottapharm Madaus
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NICCOLINI Silvia
Department of Clinical Medicine and Immunology, Rheumatology Unit
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GALEAZZI Mauro
Department of Clinical Medicine and Immunology, Rheumatology Unit
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ANZINI Maurizio
Department of Pure and Applied Medicinal Chemistry, University of Siena
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Capua Angela
Department of Pure and Applied Medicinal Chemistry, University of Siena, Italy
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Tinti Laura
Department of Clinical Medicine and Immunology, Rheumatology Unit, University of Siena, Italy
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Anzini Maurizio
Department of Pure and Applied Medicinal Chemistry, University of Siena, Italy
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Niccolini Silvia
Department of Clinical Medicine and Immunology, Rheumatology Unit, University of Siena, Italy
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Pascarelli Nicola
Department of Clinical Medicine and Immunology, Rheumatology Unit, University of Siena, Italy
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Lamboglia Antonello
Department of Clinical Medicine and Immunology, Rheumatology Unit, University of Siena, Italy
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Galeazzi Mauro
Department of Clinical Medicine and Immunology, Rheumatology Unit, University of Siena, Italy
関連論文
- In Vitro Effects of VA441, a New Selective Cyclooxygenase-2 Inhibitor, on Human Osteoarthritic Chondrocytes exposed to IL-1β
- In Vitro Effects of VA441, a New Selective Cyclooxygenase-2 Inhibitor, on Human Osteoarthritic Chondrocytes exposed to IL-1β