Inhibitory effect of auranofin (I) and chloroquine (II) on bone degradation induced by the interleukin 1-like (IL-1-like) factor released from rheumatoid synovial tissue (RAST) in vitro
RAST, maintained in organ culture, releases two distinct types of bone resorptive factors and one co-resorptive factor. The first is prostaglandin E/sub 2/ (PGE/sub 2/), while the second is a protein with properties of IL-1. The co-resorptive factor collagenase, cannot induce bone resorption by itself, but augments the bone resorptive activity initiated by either PGE/sub 2/ or the IL-l-like factor. Bone resorptive activity was assessed by measuring the release of /sup 45/Ca from prelabelled rat fetal bones. We investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) and two disease-modifying anti-rheumatic drugs (DMARDs), (I) and (II), on bone degradation mediated by the IL-l-like factor. None of the NSAIDs tested inhibited bone degradation at 5 x 10/sup -5/ M. On the other hand, both (I) and (II) inhibited bone degradation 60 to 100% at 1 x 10/sup -6/ M and 8 x 10/sup -6/ M respectively. They can inhibit the action of IL-l-like factor on bone at therapeutically attainable concentrations. Additionally, both (I) and (II) block the release of collagenase from the organ culture of RAST with IC/sub 50/s of 5 x 10/sup -6/ M. This unique ability to inhibit collagenase release may contribute to their effectiveness is preventing bone loss in this test model.
- Research Organization:
- Syntex Research, Palo Alto, CA
- OSTI ID:
- 5506717
- Report Number(s):
- CONF-8604222-; TRN: 86-026710
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIPYRETICS
BIOLOGICAL EFFECTS
SKELETON
DECOMPOSITION
CALCIUM 45
LYMPHOKINES
PEPTIDE HYDROLASES
PROSTAGLANDINS
PROTEINS
SKELETAL DISEASES
TISSUE CULTURES
TRACER TECHNIQUES
ALKALINE EARTH ISOTOPES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
GROWTH FACTORS
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MITOGENS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
550901* - Pathology- Tracer Techniques