Interleukin 6 production in fetal rat long bone cultures is correlated with PGE2 release and does not correlate with the extent of bone resorption
| Autor: | Donald R. Bertolini, Sandra J. Hoffman, Bartholomew J. Votta, Gideon Strassmann |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Immunology Long bone Parathyroid hormone Endogeny Biochemistry Bone and Bones Dinoprostone Bone resorption Embryonic and Fetal Development Organ Culture Techniques Calcitriol Internal medicine medicine Animals Immunology and Allergy Bone Resorption Interleukin 6 Molecular Biology biology Interleukin-6 Chemistry Interleukin Hematology Stimulation Chemical Rats Resorption Endocrinology medicine.anatomical_structure Parathyroid Hormone biology.protein Interleukin-1 Prostaglandin E |
| Zdroj: | Cytokine. 6:368-375 |
| ISSN: | 1043-4666 |
| Popis: | Reports from several laboratories have suggested that interleukin 6 (IL-6) may play a role in the process of bone resorption. We have extended these studies by examining the role of IL-6 in fetal rat long bone (FRLB) resorption stimulated by a variety of agents, including parathyroid hormone (PTH); 1,25 dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ); interleukin 1 (IL-1); tumour necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS). This model of bone resorption does not require the generation of osteoclasts in order to elicit a resorptive response and allowed us to assess whether IL-6 can directly affect osteoclastic bone resorption. We confirmed previous studies which showed that exogenous recombinant murine or human IL-6 does not stimulate bone resorption and demonstrated that IL-6, when added prior to the addition of parathyroid hormone, caused a significant but somewhat variable inhibition at 120 hours. Exogenous PGE 2 stimulated both IL-6 production and resorption in FRLB cultures in a concentration-dependent manner. Endogenous production of IL-6 in fetal rat long bone (FRLB) cultures was stimulus dependent and generally correlated with prostaglandin E 2 (PGE 2 ) levels in the same cultures. However, endogenous IL-6 production did not correlate with the extent of bone resorption, except when IL-1 and PGE 2 were used as stimuli. Addition of indomethacin and diclofenac to IL-1 stimulated cultures demonstrated that both the IL-6 production and bone resorption were largely PGE-2 dependent. Neutralizing anti-IL-6 antibodies inhibited IL-6 activity in FRLB cultures but did not affect bone resorption, even in the IL-1 stimulated cultures. Taken together, these data suggest that, in general, IL-6 produced by fetal rat long bones correlates with prostaglandin production and is not directly related to resorption in FRLB cultures, irrespective of the stimulus employed. However this does not exclude the possibility that IL-6 may be involved in the maturation or differentiation of osteoclasts. |
| Databáze: | OpenAIRE |
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