N. Franchimont et al., INTERLEUKIN-6 AND ITS SOLUBLE RECEPTOR CAUSE A MARKED INDUCTION OF COLLAGENASE-3 EXPRESSION IN RAT OSTEOBLAST CULTURES, The Journal of biological chemistry, 272(18), 1997, pp. 12144-12150
Interleukin-6 (IL-6), a cytokine produced by skeletal cells, increases
bone resorption, but its effects on collagenase expression are unknow
n. We tested the effects of IL-6 and its soluble receptor on collagena
se 3 expression in osteoblast enriched cells from fetal rat calvariae
(Ob cells). IL-6 caused a small increase in collagenase mRNA levels, b
ut in the presence of IL-6-soluble receptor (IL-6sR), IL-6 caused a ma
rked increase in collagenase transcripts after 2-24 h. In addition, IL
-6sR increased collagenase mRNA when tested alone. IL-6 and IL-6sR inc
reased immunoreactive collagenase levels. Cycloheximide and indomethac
in did not prevent the effect of IL-6 and IL-6sR on collagenase mRNA l
evels. IL-6 and IL-6sR did not alter the decay of collagenase mRNA in
transcriptionally arrested Ob cells and increased the levels of collag
enase heterogeneous nuclear RNA and the rate of collagenase gene trans
cription in Ob cells. IL-6 and IL-6sR increased collagenase 3 mRNA in
MC3T3 cells but only modestly in skin fibroblasts. IL-6 and IL-6sR enh
anced the expression of tissue inhibitor of metalloproteinases 1. In c
onclusion, IL-6, in the presence of IL-6sR, increases collagenase 3 sy
nthesis in osteoblasts by transcriptional mechanisms. This effect may
contribute to the action of IL-6 on bone matrix degradation and bone r
esorption.