Effect of Cytokines on Production of Insulin-like Growth Factor Binding Proteins (IGFBPs) from Human Fibroblasts in Culture.

Accession number;99A0391895
Title;Effect of Cytokines on Production of Insulin-like Growth Factor Binding Proteins (IGFBPs) from Human Fibroblasts in Culture.
Author; LIU Y (Tokyo Women's Univ., Tokyo, Jpn) TSUSHIMA T (Tokyo Women's Univ., Tokyo, Jpn) MIYAKAWA M (Tokyo Women's Univ., Tokyo, Jpn) ISOZAKI O (Beijin 514th Hospital, Beijing) YAMADA H (Tokyo Women's Univ., Tokyo, Jpn) XU Z R (Beijin 514th Hospital, Beijing) IWAMOTO Y (Tokyo Women's Univ., Tokyo, Jpn)
Journal Title;Endocr J
Journal Code:F0625A
ISSN:0918-8959
VOL.46;NO.Supplement;PAGE.S63-S66(1999)
Figure&Table&Reference;FIG.3, REF.11
Pub. Country;Japan
Language;English
Abstract;Bioactivity of Insulin-like growth factors (IGEs) are positively or negatively regulated by IGF binding proteins (IGFBPs). Like IGFs, production of IGFBPs are influenced by a number of hormonal factors. We studied the effects of cytokines on production of IGFBPs in human fibroblasts in culture. Both IL-1.BETA. and TNF-.ALPHA. inhibited IGFBP-3 (42/38 KDa species) production in a concentration dependent manner judged by Western ligand blot. Expression of IGFBP-3 mRNA was also decreased by these cytokines. Moreover, the treatment with IL-1.BETA. and TNF-.ALPHA. resulted in appearance of smaller mol weight (26 KDa) immunoreactive IGFBP-3 fragment(s) which lacked the ability to bind 125I-IGFs, indicating that these cytokines degrade IGFBP-3 via activation of proteases. Both IL-1.BETA. and TNF-.ALPHA. decreased production of IGFBP-4, whereas they increased that of IGFBP-6, IL-6 had little effect on production of IGFBPs. Likewise, interferon-.GAMMA. failed to affect of production of IGFBPs except at high concentrations. The present data demonstrate that cytokines, especially IL-1.BETA. and TNF-.ALPHA. are potent regulators of IGFBPs production and degradation. These cytokines may alter tissue uptake of IGFs and help to counteract the catabolic state induced by them. (author abst.)
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