Dependence of adaptative regulation for IL-1 beta action on system A activity in human synovial cells.
Human synovial cells are a suitable model for estimating the physiopathological effects of IL-1 beta (IL-1) in joint. Given the importance of this cytokine in the modulation of cell metabolic activities, we set out to study the action of IL-1 on the neutral amino acid transport A system, using the methyl (aminoisobutyric) acid (MeAIB), the most highly specific and nonmetabolizable substrate for the A system. Stimulation of system A activity by adaptative regulation is a prerequisite to obtain an increase of MeAIB uptake in IL-1-treated cells, since cells which had been grown in a normal medium did not express stimulation of system A activity when IL-1 was added. The IL-1-mediated MeAIB uptake is independent of protein synthesis, since cycloheximide (CHX) did not inhibit MeAIB uptake, and characterized by a decrease in the Michaelis constant K(m) (0.147 vs. 0.270 mmol/l, IL-1 vs. control) and a slight increase in maximal velocity (Vmax) (4.59 vs. 3.89 nmol/mg prot/10 min, IL-1 vs. control). These observations indicate that IL-1 induces modifications in both system A transporter affinity and number. Moreover, we indicate that system A should be responsive in vivo to IL-1 in the same way since derepression and IL-1 action occurred in the presence of human synovial fluid.
Le Maire
V
V
Laboratoire de Biochimie, Cellulaire de l'Inflammation, Université Paris Sud, Châtenay-Malabry, France.
Hernvann
A
A
Vaubourdolle
M
M
Ekindjian
O G
OG
Aussel
C
C
D000596:Amino Acids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D007717:Knee; D013583:Synovial Membrane / Q000166:cytology*; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism
D000596:Amino Acids; D007375:Interleukin-1; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine