Interleukin-1β regulation of fibroblast proteoglycan synthesis involves a decrease in versican steady-state mRNA levels

E. E. Qwarnstrom, H. T. Jarvelainen, M. G. Kinsella, C. O. Ostberg, L. J. Sandell, R. C. Page, T. N. Wight

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

This study investigates the effects of interleukin (IL)-1β on proteoglycan metabolism by fibroblasts surrounded by endogenous extracellular matrix. In both three-dimensional matrix cultures and long-term monolayer cultures IL-1β caused a significant decrease in synthesis and deposition of sulphated proteoglycans, but had no effect on release of deposited material. The decrease in synthesis became successively more pronounced, and corresponded to 40-60% of the control after 72 h incubation. The reduction was almost totally accounted for by an effect on the chondroitin ABC-lyase-sensitive proteoglycans. Gel electrophoresis showed a significant decrease in a high-molecular-mass chondroitin ABC-lyase-sensitive proteoglycan after incubation with IL-1β. Northern-blot analyses of total RNA revealed a pronounced decrease in the steady-state mRNA levels of versican, the large chondroitin sulphate, with levels corresponding to 10-30% of controls. In comparison, the steady-state mRNA level for decorin, the major sulphated proteoglycan synthesized by the cells, was only slightly affected. The prominent decrease in synthesis of sulphated proteoglycans induced in long-term fibroblast cultures, including the pronounced decrease in versican steady-state mRNA levels, is likely to have a significant effect on the structure of the extracellular matrix. Induction of this type of change may constitute a significant mechanism whereby IL-1β can affect the properties of connective tissue during inflammation and wound healing.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalBiochemical Journal
Volume294
Issue number2
DOIs
StatePublished - 1993

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