The effects of interleukin-1 on the expression of thrombospondin and fibronectin by rabbit articular chondrocytes.
Studies to evaluate the effects of recombinant interleukin-1 beta (IL-1) on the expression of matrix proteins by rabbit articular chondrocytes were conducted. Chondrocytes expressed high levels of message for thrombospondin (Tsp) and fibronectin (Fn). RNA slot-blot analysis demonstrated that treatment of the cultures with IL-1 (100 ng/ml) for 24 h caused a 70% suppression of their steady-state Tsp mRNA levels whereas those of Fn were not affected. Steady-state mRNA levels for the intracellular protein, actin, were not modulated by treatment with IL-1. The suppression of Tsp mRNA levels by IL-1 (100 ng/ml) was maximal by 4 h and was concentration dependent; half-maximal suppression was estimated to require 0.12 ng/ml IL-1. Cycloheximide treatment enhanced Tsp mRNA levels, but did not modulate IL-1 suppression of Tsp mRNA. Using pulse-labeling and immunoprecipitation techniques, we found that IL-1 suppression of Tsp mRNA levels was reflected in a coordinate inhibition of Tsp protein synthesis. Chondrocyte synthesis of Fn was not affected by IL-1. These data suggest that IL-1 specifically regulates chondrocyte expression of Tsp at least in part by decreasing the amount of Tsp mRNA available for translation.
Lyons-Giordano
B
B
DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880.
Kefalides
N A
NA
Brinker
J M
JM
Pratta
M A
MA
Arner
E C
EC
D000199:Actins / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005353:Fibronectins / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D019699:Thrombospondins
D000199:Actins; D005353:Fibronectins; D007375:Interleukin-1; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D019699:Thrombospondins; D003513:Cycloheximide