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Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine.
J Pharmacol Exp Ther. 1999 Aug; 290(2):587-93.JP

Abstract

The effects of hymenialdisine (SK&F 108752) were evaluated on interleukin-1 (IL-1)-induced proteoglycan (PG) degradation, PG synthesis, nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) gene expression in bovine articular cartilage (BAC) and/or cartilage-derived chondrocytes. Cartilage disks from 0- to 3-month-old calves were treated with IL-1alpha or retinoic acid. PG release was determined by measuring glycosaminoglycan release, and nitrite production was measured as a readout for NO. Inhibition of iNOS gene expression was measured by Northern blot analysis in IL-1alpha-stimulated, cartilage-derived chondrocytes. To measure PG synthesis, chondrocytes were established in alginate beads and treated with hymenialdisine, and then [(35)S]sulfate incorporation into PGs was determined. Hymenialdisine inhibited IL-1alpha-stimulated PG breakdown in BAC in a dose-related manner with an IC(50) of approximately 0.6 microM. Herbimycin, a protein tyrosine kinase inhibitor, also inhibited PG breakdown, whereas RO 32-0432, a protein kinase C inhibitor, had no effect. Both hymenialdisine and herbimycin also were able to inhibit retinoic acid-stimulated PG release. IL-1alpha-stimulated NO production in BAC was inhibited by hymenialdisine and herbimycin at similar concentrations. The effect on iNOS gene expression was determined by Northern blot analysis in chondrocytes grown in monolayer, and inhibition by hymenialdisine was observed with an IC(50) of approximately 0.8 microM. In chondrocytes cultured in alginate beads, IL-1alpha inhibited PG synthesis, whereas hymenialdisine stimulated synthesis at low concentrations (0.6 and 1.25 microM), and higher doses (2.5 microM) were not stimulatory. Compounds with this profile may have utility in the treatment of osteoarthritis.

Authors+Show Affiliations

Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA. Allison_M_Badger@SBPHRD.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10411566

Citation

Badger, A M., et al. "Inhibition of Interleukin-1-induced Proteoglycan Degradation and Nitric Oxide Production in Bovine Articular Cartilage/chondrocyte Cultures By the Natural Product, Hymenialdisine." The Journal of Pharmacology and Experimental Therapeutics, vol. 290, no. 2, 1999, pp. 587-93.
Badger AM, Cook MN, Swift BA, et al. Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine. J Pharmacol Exp Ther. 1999;290(2):587-93.
Badger, A. M., Cook, M. N., Swift, B. A., Newman-Tarr, T. M., Gowen, M., & Lark, M. (1999). Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine. The Journal of Pharmacology and Experimental Therapeutics, 290(2), 587-93.
Badger AM, et al. Inhibition of Interleukin-1-induced Proteoglycan Degradation and Nitric Oxide Production in Bovine Articular Cartilage/chondrocyte Cultures By the Natural Product, Hymenialdisine. J Pharmacol Exp Ther. 1999;290(2):587-93. PubMed PMID: 10411566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine. AU - Badger,A M, AU - Cook,M N, AU - Swift,B A, AU - Newman-Tarr,T M, AU - Gowen,M, AU - Lark,M, PY - 1999/7/20/pubmed PY - 1999/7/20/medline PY - 1999/7/20/entrez SP - 587 EP - 93 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 290 IS - 2 N2 - The effects of hymenialdisine (SK&F 108752) were evaluated on interleukin-1 (IL-1)-induced proteoglycan (PG) degradation, PG synthesis, nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) gene expression in bovine articular cartilage (BAC) and/or cartilage-derived chondrocytes. Cartilage disks from 0- to 3-month-old calves were treated with IL-1alpha or retinoic acid. PG release was determined by measuring glycosaminoglycan release, and nitrite production was measured as a readout for NO. Inhibition of iNOS gene expression was measured by Northern blot analysis in IL-1alpha-stimulated, cartilage-derived chondrocytes. To measure PG synthesis, chondrocytes were established in alginate beads and treated with hymenialdisine, and then [(35)S]sulfate incorporation into PGs was determined. Hymenialdisine inhibited IL-1alpha-stimulated PG breakdown in BAC in a dose-related manner with an IC(50) of approximately 0.6 microM. Herbimycin, a protein tyrosine kinase inhibitor, also inhibited PG breakdown, whereas RO 32-0432, a protein kinase C inhibitor, had no effect. Both hymenialdisine and herbimycin also were able to inhibit retinoic acid-stimulated PG release. IL-1alpha-stimulated NO production in BAC was inhibited by hymenialdisine and herbimycin at similar concentrations. The effect on iNOS gene expression was determined by Northern blot analysis in chondrocytes grown in monolayer, and inhibition by hymenialdisine was observed with an IC(50) of approximately 0.8 microM. In chondrocytes cultured in alginate beads, IL-1alpha inhibited PG synthesis, whereas hymenialdisine stimulated synthesis at low concentrations (0.6 and 1.25 microM), and higher doses (2.5 microM) were not stimulatory. Compounds with this profile may have utility in the treatment of osteoarthritis. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10411566/Inhibition_of_interleukin_1_induced_proteoglycan_degradation_and_nitric_oxide_production_in_bovine_articular_cartilage/chondrocyte_cultures_by_the_natural_product_hymenialdisine_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10411566 DB - PRIME DP - Unbound Medicine ER -