Effects of interleukin-1 beta on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes.
OBJECTIVE
To clarify the interaction of tissue destruction and repair of articular cartilage during inflammation, the effects of interleukin-1 beta (IL-1 beta) on the expression of insulin-like growth factor I (IGF-I), its receptor, and its binding proteins were examined.


METHODS
Articular chondrocytes from five week rats were cultured in serum free medium treated with IL-1 beta (1-100 U/ml) for 24 hours. The concentration of IGF-1 in the conditioned medium was measured by RIA, and IGFBP were analysed by immunoligand blotting method. IGF-I receptors were also examined by [125I]IGF-I binding study.


RESULTS
IL-1 beta induced the secretion of IGF-I and IGF-binding protein in chondrocytes; this was not inhibited by indomethacin (5 micrograms/ml). IL-1 beta also increased the number of IGF-I receptors but had no effect on receptor affinity. IL-1 beta inhibited chondrocyte proliferation, while exogenous IGF-I and growth hormone stimulated chondrocyte cell growth. IL-1 beta did not change IGF-I mRNA levels.


CONCLUSIONS
IL-1 beta up-regulated the IGF-I autocrine/paracrine axis in cultured articular chondrocytes. These observations provide insight into the critical role played by IL-1 beta in tissue destruction and repair, and into the direct interaction between cytokines and growth factors associated with inflammatory arthropathy.
Matsumoto
T
T
Department of Orthopedic Surgery, Nagasaki University School of Medicine, Japan.
Tsukazaki
T
T
Enomoto
H
H
Iwasaki
K
K
Yamashita
S
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D007375:Interleukin-1; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D007213:Indomethacin