Platelet-derived growth factor potentiates cellular responses of articular chondrocytes to interleukin-1.
Recombinant human interleukin-1 alpha (IL-1 alpha) induced a time-dependent (0-72 hours) and concentration-dependent (0.01-10 ng/ml) production of metalloproteinases (collagenase, gelatinase, stromelysin) and prostaglandin E2 (PGE2) in rabbit articular chondrocytes (RAC). Exposure of RAC to recombinant human platelet-derived growth factor homodimer BB (PDGF-BB; 2-200 ng/ml) in the presence of stimulatory and substimulatory concentrations of IL-1 alpha resulted in a marked augmentation of metalloproteinase and PGE2 production. PDGF-BB exerted no agonist effects on RAC responsiveness. PDGF-BB up-regulated the number of IL-1 receptors per chondrocyte but had no effect on receptor affinity. Cycloheximide and actinomycin D caused a concentration-dependent suppression of the PDGF-BB-mediated potentiation of radiolabeled IL-1 alpha binding to RAC and cell responsiveness to IL-1 alpha. Similarly, IL-1 increased the number of PDGF receptors on RAC without changing receptor affinity. These data are discussed within the context of cytokine-growth factor interactions as components of the pathogenesis of arthritic diseases.
Smith
R J
RJ
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Justen
J M
JM
Sam
L M
LM
Rohloff
N A
NA
Ruppel
P L
PL
Brunden
M N
MN
Chin
J E
JE
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D003609:Dactinomycin; D003513:Cycloheximide; D008666:Metalloendopeptidases; D015232:Dinoprostone