Granulocyte-macrophage colony stimulating factor is anabolic and interleukin-1beta is catabolic for rat articular chondrocytes.
OBJECTIVE
To study the effects of GM-CSF and IL-1beta, both implicated in tissue damage in arthritis, on articular chondrocyte proliferation and metabolism, and to explore their agonist/antagonist effects.


METHODS
Chondrocytes were obtained from 1-month-old rats. First-passage monolayers were incubated for 24 h with or without GM-CSF and/or IL-1beta, and labeled with 3H-thymidine, 35S-SO4 and 14C-proline. Proteoglycan and collagen synthesis were analyzed by liquid chromatography and SDS-PAGE. Gene expression was measured by RT-PCR.


RESULTS
IL-1beta exerts potent, and GM-CSF weak, inhibitory effects on DNA synthesis. GM-CSF strongly stimulates, and IL-1beta inhibits, proteoglycan and collagen synthesis. IL-1beta suppresses the effect of GM-CSF, and increases the release of radioactive molecules from pre-labeled cartilage fragments; GM-CSF decreases the IL-1beta-induced effect. Interestingly, both cytokines induce the expression of each other's gene.


CONCLUSIONS
IL-1beta appears to be a catabolic and anti-anabolic agent for chondrocytes, whereas GM-CSF is mainly anabolic, and blocks the IL-1beta-induced catabolic effect. It is postulated that both agents are implicated in inflammation: IL-1beta promotes tissue catabolism and destruction, whereas GM-CSF enhances tissue reconstruction.
Quintero
Maritza
M
Inserm U606, Lariboisiere Hospital, Paris, France. maritzaquintero@gmail.com
Riera
Humberto
H
Colantuoni
Gladys
G
Khatib
Abdel-Majid
AM
Attalah
Habiba
H
Moldovan
Florina
F
Mitrovic
Dragoslav R
DR
Lomri
Abderrahim
A
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D053583:Interleukin-1beta; D011509:Proteoglycans; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen; D004247:DNA