Different inhibitory actions of cyclosporine A and cyclosporine A-acetate on lipopolysaccharide-, interleukin 1-, 1,25 dihydroxyvitamin D3- and parathyroid hormone-stimulated calcium and lysosomal enzyme release from mouse calvaria in vitro.
The effects of cyclosporine A (CsA) and one of its immunologically inactive structural analogues, cyclosporine A acetate (CsA-A) on lipopolysaccharide (LPS)-, interleukin-1 (IL-1)-, 1,25 dihydroxyvitamin D3 (1,25 D3)- and parathyroid hormone (PTH)-stimulated bone resorption were tested in mouse calvaria cultures. The release of calcium and a lysosomal enzyme, N-acetylglycosaminidase (NAG) was determined after 3 days of culture. All bone resorbing agents potently stimulated calcium and NAG release. At therapeutic concentration levels of 0.1 and 1.0 micrograms/ml, the immunologically active CsA was significantly more potent than the inactive CsA-A against LPS- and 1,25 D3-induced calcium and NAG release. The inhibition by both cyclosporines of IL-1 and PTH stimulated calcium release was not significantly different. CsA was however more potent than CsA-A against IL-1 stimulated NAG release. PTH-stimulated NAG release was not inhibited by CsA or CsA-A. These findings suggest that both cyclosporines interfere with more than one mechanism of activation of bone resorption. The specific effect of CsA against LPS and 1,25 D3 may be related to its known inhibition of immune cell derived cytokine expression.
Tullberg-Reinert
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Dental Institute, University of Basle, Switzerland.
Hefti
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D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004396:Coloring Agents; D003524:Cyclosporins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D010281:Parathyroid Hormone / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012475:Salmonella; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D003524:Cyclosporins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C065699:SDZ 33-243; D000118:Acetylglucosaminidase; C022616:thiazolyl blue; D002117:Calcitriol; D002118:Calcium